NM_001048174.2:c.-60C>A

Variant names:

• chr1-45339952-G-T
• rs185172591
• NM_001048174.2:c.-60C>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001048174.2(MUTYH):​c.-60C>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000746 in 1,341,342 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 7.5e-7 (0 hom.)
• Consequence: MUTYH NM_001048174.2 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -4.76
• 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]

ENSG00000288208 (HGNC:):

TOE1 (HGNC:15954): (target of EGR1, exonuclease) Enables poly(A)-specific ribonuclease activity and snRNA binding activity. Involved in RNA phosphodiester bond hydrolysis, exonucleolytic and snRNA 3'-end processing. Located in Cajal body and cytoplasm. Implicated in pontocerebellar hypoplasia type 7. [provided by Alliance of Genome Resources, Apr 2022]

TOE1 Gene-Disease associations (from GenCC):

• pontocerebellar hypoplasia type 7

  Inheritance: AR Classification: STRONG, MODERATE, SUPPORTIVE Submitted by: Ambry Genetics, PanelApp Australia, Labcorp Genetics (formerly Invitae), Orphanet, G2P

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001048174.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MUTYH	NM_001048174.2	MANE Select	c.-60C>A		5_prime_UTR	Exon 1 of 16	NP_001041639.1	Q9UIF7-6
	MUTYH	NM_001128425.2	MANE Plus Clinical	c.36+267C>A		intron	N/A	NP_001121897.1	E5KP25
	MUTYH	NM_001407085.1		c.-60C>A		5_prime_UTR	Exon 1 of 16	NP_001394014.1	E9PM53

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MUTYH	ENST00000456914.7	TSL:1 MANE Select	c.-60C>A		5_prime_UTR	Exon 1 of 16	ENSP00000407590.2	Q9UIF7-6
	MUTYH	ENST00000710952.2	MANE Plus Clinical	c.36+267C>A		intron	N/A	ENSP00000518552.2	E5KP25
	MUTYH	ENST00000372098.7	TSL:1	c.36+267C>A		intron	N/A	ENSP00000361170.3	Q9UIF7-1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 7.46e-7 AC: 1 AN: 1341342 Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0 AN XY: 661522

African (AFR) AF: 0.00 AC: 0 AN: 30644

American (AMR) AF: 0.00 AC: 0 AN: 34626

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 23396

East Asian (EAS) AF: 0.00 AC: 0 AN: 30802

South Asian (SAS) AF: 0.00 AC: 0 AN: 78714

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40982

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5380

European-Non Finnish (NFE) AF: 9.59e-7 AC: 1 AN: 1042516

Other (OTH) AF: 0.00 AC: 0 AN: 54282

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	0.59
DANN	Benign	0.51
PhyloP100		-4.8
PromoterAI		-0.14	Neutral

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		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: rs185172591; hg19: chr1-45805624;