1-45331444-G-C

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 2P and 13B. PM2BP4_StrongBP6_Very_StrongBP7

The NM_001048174.2(MUTYH):ā€‹c.1215C>Gā€‹(p.Ala405=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,882 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (ā˜…ā˜…).

Frequency

Genomes: not found (cov: 33)
Exomes š‘“: 0.0000014 ( 0 hom. )

Consequence

MUTYH
NM_001048174.2 synonymous

Scores

2

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -1.48
Variant links:
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]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -11 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.86).
BP6
Variant 1-45331444-G-C is Benign according to our data. Variant chr1-45331444-G-C is described in ClinVar as [Likely_benign]. Clinvar id is 492009.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
Synonymous conserved (PhyloP=-1.48 with no splicing effect.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
MUTYHNM_001128425.2 linkuse as main transcriptc.1299C>G p.Ala433= synonymous_variant 13/16 ENST00000710952.2
MUTYHNM_001048174.2 linkuse as main transcriptc.1215C>G p.Ala405= synonymous_variant 13/16 ENST00000456914.7

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
MUTYHENST00000710952.2 linkuse as main transcriptc.1299C>G p.Ala433= synonymous_variant 13/16 NM_001128425.2
MUTYHENST00000456914.7 linkuse as main transcriptc.1215C>G p.Ala405= synonymous_variant 13/161 NM_001048174.2 A1Q9UIF7-6

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
AF:
0.00000137
AC:
2
AN:
1461882
Hom.:
0
Cov.:
33
AF XY:
0.00000275
AC XY:
2
AN XY:
727240
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000232
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
33

ClinVar

Significance: Likely benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

Familial adenomatous polyposis 2 Benign:1
Likely benign, criteria provided, single submitterclinical testingInvitaeJan 09, 2024- -
Hereditary cancer-predisposing syndrome Benign:1
Likely benign, criteria provided, single submitterclinical testingColor Diagnostics, LLC DBA Color HealthJun 19, 2017- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.86
CADD
Benign
0.55
DANN
Benign
0.56

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs1553125605; hg19: chr1-45797116; API