rs75321043

Variant summary

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

The NM_001048174.2(MUTYH):​c.32G>T​(p.Gly11Val) 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. 14/21 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. G11D) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 32)

Consequence

MUTYH
NM_001048174.2 missense

Scores

1
3
15

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.25
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=0.093682796).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
MUTYHNM_001128425.2 linkuse as main transcriptc.74G>T p.Gly25Val missense_variant 2/16 ENST00000710952.2 NP_001121897.1
MUTYHNM_001048174.2 linkuse as main transcriptc.32G>T p.Gly11Val missense_variant 2/16 ENST00000456914.7 NP_001041639.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
MUTYHENST00000710952.2 linkuse as main transcriptc.74G>T p.Gly25Val missense_variant 2/16 NM_001128425.2 ENSP00000518552
MUTYHENST00000456914.7 linkuse as main transcriptc.32G>T p.Gly11Val missense_variant 2/161 NM_001048174.2 ENSP00000407590 A1Q9UIF7-6

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Cov.:
31
GnomAD4 genome
Cov.:
32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.099
BayesDel_addAF
Benign
-0.089
T
BayesDel_noAF
Benign
-0.37
CADD
Benign
18
DANN
Uncertain
0.99
DEOGEN2
Benign
0.11
.;.;.;.;.;.;T;.;.;.;.;.;T;T;T
Eigen
Benign
-0.29
Eigen_PC
Benign
-0.37
FATHMM_MKL
Benign
0.24
N
LIST_S2
Uncertain
0.90
.;.;D;.;D;D;D;D;D;D;D;D;D;D;D
M_CAP
Benign
0.021
T
MetaRNN
Benign
0.094
T;T;T;T;T;T;T;T;T;T;T;T;T;T;T
MetaSVM
Uncertain
-0.20
T
MutationAssessor
Benign
1.3
.;.;.;.;.;.;L;L;L;.;.;.;.;.;.
MutationTaster
Benign
1.0
N;N;N;N;N;N;N;N;N;N;N;N;N;N
PrimateAI
Benign
0.22
T
PROVEAN
Benign
0.15
N;N;N;N;N;N;N;N;N;N;N;D;N;N;N
REVEL
Benign
0.051
Sift
Benign
0.047
D;D;D;D;D;D;D;D;D;D;D;D;D;D;D
Sift4G
Pathogenic
0.0
D;D;T;D;D;D;T;D;D;D;T;T;T;T;T
Polyphen
0.88, 0.93, 0.34
.;.;.;.;.;.;P;P;.;.;B;.;.;.;.
Vest4
0.25
MutPred
0.25
.;.;.;.;.;.;Loss of relative solvent accessibility (P = 0.0071);Loss of relative solvent accessibility (P = 0.0071);Loss of relative solvent accessibility (P = 0.0071);.;Loss of relative solvent accessibility (P = 0.0071);.;.;.;.;
MVP
0.81
MPC
0.21
ClinPred
0.28
T
GERP RS
2.9
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.1
Varity_R
0.061
gMVP
0.21

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr1-45800146; API