rs878854183

Variant names:

• chr1-45331691-G-A
• rs878854183
• NM_001048174.2:c.1072C>T

Your query was ambiguous. Multiple possible variants found:

• chr1-45331691-G-A
• chr1-45331691-G-C

Variant summary

Our verdict is Pathogenic. The variant received 12 ACMG points: 12P and 0B. PVS1 PM2 PP5_Moderate

The NM_001048174.2(MUTYH):​c.1072C>T​(p.Gln358*) variant causes a stop gained change. The variant allele was found at a frequency of 0.000000684 in 1,461,696 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Pathogenic (★). Variant results in nonsense mediated mRNA decay.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: MUTYH NM_001048174.2 stop_gained
• Clinical Significance: Pathogenic criteria provided, single submitter P:1
• Conservation: PhyloP100: 3.66
• Publications: 0 publications found

Genes affected

MUTYH (HGNC:7527): (mutY DNA glycosylase) This gene encodes a DNA glycosylase involved in oxidative DNA damage repair. The enzyme excises adenine bases from the DNA backbone at sites where adenine is inappropriately paired with guanine, cytosine, or 8-oxo-7,8-dihydroguanine, a major oxidatively damaged DNA lesion. The protein is localized to the nucleus and mitochondria. This gene product is thought to play a role in signaling apoptosis by the introduction of single-strand breaks following oxidative damage. Mutations in this gene result in heritable predisposition to colorectal cancer, termed MUTYH-associated polyposis (MAP). Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Apr 2017]

MUTYH Gene-Disease associations (from GenCC):

• familial adenomatous polyposis 2

  Inheritance: AD, AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Orphanet, Labcorp Genetics (formerly Invitae), Genomics England PanelApp, ClinGen, G2P
• colorectal cancer

  Inheritance: AD Classification: NO_KNOWN Submitted by: ClinGen
• familial ovarian cancer

  Inheritance: AD, AR Classification: NO_KNOWN Submitted by: ClinGen
• hereditary breast carcinoma

  Inheritance: AD, AR Classification: NO_KNOWN Submitted by: ClinGen

ENSG00000288208 (HGNC:):

ACMG classification

Our verdict: Pathogenic. The variant received 12 ACMG points.

• PVS1: Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
• PM2: Very rare variant in population databases, with high coverage
• PP5: Variant 1-45331691-G-A is Pathogenic according to our data. Variant chr1-45331691-G-A is described in CliVar as Pathogenic. Clinvar id is 2453360.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr1-45331691-G-A is described in CliVar as Pathogenic. Clinvar id is 2453360.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr1-45331691-G-A is described in CliVar as Pathogenic. Clinvar id is 2453360.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr1-45331691-G-A is described in CliVar as Pathogenic. Clinvar id is 2453360.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr1-45331691-G-A is described in CliVar as Pathogenic. Clinvar id is 2453360.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr1-45331691-G-A is described in CliVar as Pathogenic. Clinvar id is 2453360.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr1-45331691-G-A is described in CliVar as Pathogenic. Clinvar id is 2453360.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr1-45331691-G-A is described in CliVar as Pathogenic. Clinvar id is 2453360.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr1-45331691-G-A is described in CliVar as Pathogenic. Clinvar id is 2453360.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr1-45331691-G-A is described in CliVar as Pathogenic. Clinvar id is 2453360.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr1-45331691-G-A is described in CliVar as Pathogenic. Clinvar id is 2453360.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr1-45331691-G-A is described in CliVar as Pathogenic. Clinvar id is 2453360.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr1-45331691-G-A is described in CliVar as Pathogenic. Clinvar id is 2453360.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr1-45331691-G-A is described in CliVar as Pathogenic. Clinvar id is 2453360.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr1-45331691-G-A is described in CliVar as Pathogenic. Clinvar id is 2453360.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr1-45331691-G-A is described in CliVar as Pathogenic. Clinvar id is 2453360.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr1-45331691-G-A is described in CliVar as Pathogenic. Clinvar id is 2453360.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr1-45331691-G-A is described in CliVar as Pathogenic. Clinvar id is 2453360.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr1-45331691-G-A is described in CliVar as Pathogenic. Clinvar id is 2453360.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr1-45331691-G-A is described in CliVar as Pathogenic. Clinvar id is 2453360.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr1-45331691-G-A is described in CliVar as Pathogenic. Clinvar id is 2453360.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr1-45331691-G-A is described in CliVar as Pathogenic. Clinvar id is 2453360.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr1-45331691-G-A is described in CliVar as Pathogenic. Clinvar id is 2453360.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr1-45331691-G-A is described in CliVar as Pathogenic. Clinvar id is 2453360.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr1-45331691-G-A is described in CliVar as Pathogenic. Clinvar id is 2453360.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr1-45331691-G-A is described in CliVar as Pathogenic. Clinvar id is 2453360.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr1-45331691-G-A is described in CliVar as Pathogenic. Clinvar id is 2453360.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr1-45331691-G-A is described in CliVar as Pathogenic. Clinvar id is 2453360.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr1-45331691-G-A is described in CliVar as Pathogenic. Clinvar id is 2453360.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr1-45331691-G-A is described in CliVar as Pathogenic. Clinvar id is 2453360.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr1-45331691-G-A is described in CliVar as Pathogenic. Clinvar id is 2453360.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr1-45331691-G-A is described in CliVar as Pathogenic. Clinvar id is 2453360.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr1-45331691-G-A is described in CliVar as Pathogenic. Clinvar id is 2453360.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr1-45331691-G-A is described in CliVar as Pathogenic. Clinvar id is 2453360.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr1-45331691-G-A is described in CliVar as Pathogenic. Clinvar id is 2453360.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr1-45331691-G-A is described in CliVar as Pathogenic. Clinvar id is 2453360.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr1-45331691-G-A is described in CliVar as Pathogenic. Clinvar id is 2453360.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr1-45331691-G-A is described in CliVar as Pathogenic. Clinvar id is 2453360.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr1-45331691-G-A is described in CliVar as Pathogenic. Clinvar id is 2453360.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr1-45331691-G-A is described in CliVar as Pathogenic. Clinvar id is 2453360.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr1-45331691-G-A is described in CliVar as Pathogenic. Clinvar id is 2453360.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr1-45331691-G-A is described in CliVar as Pathogenic. Clinvar id is 2453360.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr1-45331691-G-A is described in CliVar as Pathogenic. Clinvar id is 2453360.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr1-45331691-G-A is described in CliVar as Pathogenic. Clinvar id is 2453360.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr1-45331691-G-A is described in CliVar as Pathogenic. Clinvar id is 2453360.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr1-45331691-G-A is described in CliVar as Pathogenic. Clinvar id is 2453360.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr1-45331691-G-A is described in CliVar as Pathogenic. Clinvar id is 2453360.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr1-45331691-G-A is described in CliVar as Pathogenic. Clinvar id is 2453360.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr1-45331691-G-A is described in CliVar as Pathogenic. Clinvar id is 2453360.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr1-45331691-G-A is described in CliVar as Pathogenic. Clinvar id is 2453360.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr1-45331691-G-A is described in CliVar as Pathogenic. Clinvar id is 2453360.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr1-45331691-G-A is described in CliVar as Pathogenic. Clinvar id is 2453360.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr1-45331691-G-A is described in CliVar as Pathogenic. Clinvar id is 2453360.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr1-45331691-G-A is described in CliVar as Pathogenic. Clinvar id is 2453360.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr1-45331691-G-A is described in CliVar as Pathogenic. Clinvar id is 2453360.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr1-45331691-G-A is described in CliVar as Pathogenic. Clinvar id is 2453360.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr1-45331691-G-A is described in CliVar as Pathogenic. Clinvar id is 2453360.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr1-45331691-G-A is described in CliVar as Pathogenic. Clinvar id is 2453360.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr1-45331691-G-A is described in CliVar as Pathogenic. Clinvar id is 2453360.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr1-45331691-G-A is described in CliVar as Pathogenic. Clinvar id is 2453360.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr1-45331691-G-A is described in CliVar as Pathogenic. Clinvar id is 2453360.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr1-45331691-G-A is described in CliVar as Pathogenic. Clinvar id is 2453360.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr1-45331691-G-A is described in CliVar as Pathogenic. Clinvar id is 2453360.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr1-45331691-G-A is described in CliVar as Pathogenic. Clinvar id is 2453360.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr1-45331691-G-A is described in CliVar as Pathogenic. Clinvar id is 2453360.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr1-45331691-G-A is described in CliVar as Pathogenic. Clinvar id is 2453360.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr1-45331691-G-A is described in CliVar as Pathogenic. Clinvar id is 2453360.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr1-45331691-G-A is described in CliVar as Pathogenic. Clinvar id is 2453360.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr1-45331691-G-A is described in CliVar as Pathogenic. Clinvar id is 2453360.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr1-45331691-G-A is described in CliVar as Pathogenic. Clinvar id is 2453360.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr1-45331691-G-A is described in CliVar as Pathogenic. Clinvar id is 2453360.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr1-45331691-G-A is described in CliVar as Pathogenic. Clinvar id is 2453360.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr1-45331691-G-A is described in CliVar as Pathogenic. Clinvar id is 2453360.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr1-45331691-G-A is described in CliVar as Pathogenic. Clinvar id is 2453360.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr1-45331691-G-A is described in CliVar as Pathogenic. Clinvar id is 2453360.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr1-45331691-G-A is described in CliVar as Pathogenic. Clinvar id is 2453360.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr1-45331691-G-A is described in CliVar as Pathogenic. Clinvar id is 2453360.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr1-45331691-G-A is described in CliVar as Pathogenic. Clinvar id is 2453360.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr1-45331691-G-A is described in CliVar as Pathogenic. Clinvar id is 2453360.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr1-45331691-G-A is described in CliVar as Pathogenic. Clinvar id is 2453360.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr1-45331691-G-A is described in CliVar as Pathogenic. Clinvar id is 2453360.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr1-45331691-G-A is described in CliVar as Pathogenic. Clinvar id is 2453360.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr1-45331691-G-A is described in CliVar as Pathogenic. Clinvar id is 2453360.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr1-45331691-G-A is described in CliVar as Pathogenic. Clinvar id is 2453360.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr1-45331691-G-A is described in CliVar as Pathogenic. Clinvar id is 2453360.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr1-45331691-G-A is described in CliVar as Pathogenic. Clinvar id is 2453360.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr1-45331691-G-A is described in CliVar as Pathogenic. Clinvar id is 2453360.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr1-45331691-G-A is described in CliVar as Pathogenic. Clinvar id is 2453360.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr1-45331691-G-A is described in CliVar as Pathogenic. Clinvar id is 2453360.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr1-45331691-G-A is described in CliVar as Pathogenic. Clinvar id is 2453360.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr1-45331691-G-A is described in CliVar as Pathogenic. Clinvar id is 2453360.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr1-45331691-G-A is described in CliVar as Pathogenic. Clinvar id is 2453360.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr1-45331691-G-A is described in CliVar as Pathogenic. Clinvar id is 2453360.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr1-45331691-G-A is described in CliVar as Pathogenic. Clinvar id is 2453360.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr1-45331691-G-A is described in CliVar as Pathogenic. Clinvar id is 2453360.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr1-45331691-G-A is described in CliVar as Pathogenic. Clinvar id is 2453360.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr1-45331691-G-A is described in CliVar as Pathogenic. Clinvar id is 2453360.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr1-45331691-G-A is described in CliVar as Pathogenic. Clinvar id is 2453360.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr1-45331691-G-A is described in CliVar as Pathogenic. Clinvar id is 2453360.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr1-45331691-G-A is described in CliVar as Pathogenic. Clinvar id is 2453360.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr1-45331691-G-A is described in CliVar as Pathogenic. Clinvar id is 2453360.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr1-45331691-G-A is described in CliVar as Pathogenic. Clinvar id is 2453360.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr1-45331691-G-A is described in CliVar as Pathogenic. Clinvar id is 2453360.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr1-45331691-G-A is described in CliVar as Pathogenic. Clinvar id is 2453360.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr1-45331691-G-A is described in CliVar as Pathogenic. Clinvar id is 2453360.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr1-45331691-G-A is described in CliVar as Pathogenic. Clinvar id is 2453360.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr1-45331691-G-A is described in CliVar as Pathogenic. Clinvar id is 2453360.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr1-45331691-G-A is described in CliVar as Pathogenic. Clinvar id is 2453360.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr1-45331691-G-A is described in CliVar as Pathogenic. Clinvar id is 2453360.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr1-45331691-G-A is described in CliVar as Pathogenic. Clinvar id is 2453360.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr1-45331691-G-A is described in CliVar as Pathogenic. Clinvar id is 2453360.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr1-45331691-G-A is described in CliVar as Pathogenic. Clinvar id is 2453360.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr1-45331691-G-A is described in CliVar as Pathogenic. Clinvar id is 2453360.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr1-45331691-G-A is described in CliVar as Pathogenic. Clinvar id is 2453360.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MUTYH	NM_001048174.2	c.1072C>T	p.Gln358*	stop_gained	Exon 12 of 16	ENST00000456914.7	NP_001041639.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MUTYH	ENST00000456914.7	c.1072C>T	p.Gln358*	stop_gained	Exon 12 of 16	1	NM_001048174.2	ENSP00000407590.2
ENSG00000288208	ENST00000671898.1	n.1660C>T		non_coding_transcript_exon_variant	Exon 16 of 21			ENSP00000499896.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461696 Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0 AN XY: 727146

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53230

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1112006

Other (OTH) AF: 0.0000166 AC: 1 AN: 60394

GnomAD4 genome Cov.: 33

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: criteria provided, single submitter

Submissions by phenotype

Hereditary cancer-predisposing syndrome Pathogenic:1

Jan 26, 2023

Ambry Genetics

Significance: Pathogenic

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The p.Q386* pathogenic mutation (also known as c.1156C>T), located in coding exon 12 of the MUTYH gene, results from a C to T substitution at nucleotide position 1156. This changes the amino acid from a glutamine to a stop codon within coding exon 12. This variant is considered to be rare based on population cohorts in the Genome Aggregation Database (gnomAD). This alteration is expected to result in loss of function by premature protein truncation or nonsense-mediated mRNA decay. As such, this alteration is interpreted as a disease-causing mutation. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Pathogenic	0.38	D
BayesDel_noAF	Pathogenic	0.31
CADD	Pathogenic	36
DANN	Uncertain	0.99
Eigen	Pathogenic	0.70
Eigen_PC	Uncertain	0.48
FATHMM_MKL	Uncertain	0.87	D
PhyloP100		3.7
Vest4		0.91
GERP RS		4.9
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=5/195	disease causing (fs/PTC)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.060		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs878854183; hg19: chr1-45797363; COSMIC: COSV106459012;