chr1-45331753-T-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001048174.2(MUTYH):​c.1010A>G​(p.Lys337Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. K337M) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 33)

Consequence

MUTYH
NM_001048174.2 missense

Scores

19

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.349
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 Uncertain_significance. Variant got 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.08669105).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
MUTYHNM_001048174.2 linkc.1010A>G p.Lys337Arg missense_variant 12/16 ENST00000456914.7 NP_001041639.1 Q9UIF7-6

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
MUTYHENST00000456914.7 linkc.1010A>G p.Lys337Arg missense_variant 12/161 NM_001048174.2 ENSP00000407590.2 Q9UIF7-6
ENSG00000288208ENST00000671898.1 linkn.1598A>G non_coding_transcript_exon_variant 16/21 ENSP00000499896.1 A0A5F9ZGZ0

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
Cov.:
33
GnomAD4 genome
Cov.:
33
Alfa
AF:
0.0000468
Hom.:
0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.069
BayesDel_addAF
Benign
-0.12
T
BayesDel_noAF
Benign
-0.41
CADD
Benign
1.6
DANN
Benign
0.71
DEOGEN2
Benign
0.097
.;.;.;.;.;T;.;.;.;T;.
Eigen
Benign
-1.5
Eigen_PC
Benign
-1.7
FATHMM_MKL
Benign
0.26
N
LIST_S2
Benign
0.72
.;T;.;T;T;T;T;T;T;T;T
M_CAP
Benign
0.057
D
MetaRNN
Benign
0.087
T;T;T;T;T;T;T;T;T;T;T
MetaSVM
Benign
-0.88
T
MutationAssessor
Benign
1.3
.;.;.;.;.;L;.;.;.;.;.
PrimateAI
Benign
0.33
T
PROVEAN
Benign
-1.1
N;N;N;N;N;N;N;N;N;.;N
REVEL
Benign
0.28
Sift
Benign
0.42
T;T;T;T;T;T;T;T;T;.;T
Sift4G
Benign
0.28
T;T;T;T;T;T;T;T;T;T;T
Polyphen
0.0, 0.0030, 0.0020
.;.;.;.;.;B;B;.;B;.;.
Vest4
0.066
MutPred
0.23
.;.;.;.;.;.;.;.;Loss of glycosylation at K365 (P = 0.0491);.;.;
MVP
0.58
MPC
0.095
ClinPred
0.063
T
GERP RS
-11
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
Varity_R
0.059
gMVP
0.46

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.010
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: rs1553126588; hg19: chr1-45797425; API