2-189854621-A-G

Variant summary

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

The NM_000534.5(PMS1):​c.1349A>G​(p.Gln450Arg) 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. 16/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 32)

Consequence

PMS1
NM_000534.5 missense

Scores

1
18

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.02
Variant links:
Genes affected
PMS1 (HGNC:9121): (PMS1 homolog 1, mismatch repair system component) This gene encodes a protein belonging to the DNA mismatch repair mutL/hexB family. This protein is thought to be involved in the repair of DNA mismatches, and it can form heterodimers with MLH1, a known DNA mismatch repair protein. Mutations in this gene cause hereditary nonpolyposis colorectal cancer type 3 (HNPCC3) either alone or in combination with mutations in other genes involved in the HNPCC phenotype, which is also known as Lynch syndrome. [provided by RefSeq, Jul 2008]

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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=0.12542555).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
PMS1NM_000534.5 linkc.1349A>G p.Gln450Arg missense_variant 9/13 ENST00000441310.7 NP_000525.1 P54277-1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
PMS1ENST00000441310.7 linkc.1349A>G p.Gln450Arg missense_variant 9/131 NM_000534.5 ENSP00000406490.3 P54277-1

Frequencies

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

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.076
BayesDel_addAF
Benign
-0.021
T
BayesDel_noAF
Benign
-0.27
CADD
Benign
7.1
DANN
Benign
0.97
DEOGEN2
Benign
0.036
T;T;T;T;T;.;.;.;.
Eigen
Benign
-0.62
Eigen_PC
Benign
-0.78
FATHMM_MKL
Benign
0.20
N
LIST_S2
Benign
0.61
T;.;T;T;T;T;T;T;T
M_CAP
Benign
0.044
D
MetaRNN
Benign
0.13
T;T;T;T;T;T;T;T;T
MetaSVM
Uncertain
0.23
D
MutationAssessor
Benign
1.7
.;.;.;.;L;.;L;.;.
PrimateAI
Benign
0.28
T
PROVEAN
Benign
-0.84
.;.;N;.;N;N;N;N;N
REVEL
Benign
0.24
Sift
Benign
0.082
.;.;T;.;T;T;T;T;T
Sift4G
Benign
0.19
.;T;T;T;T;T;T;T;T
Polyphen
0.040, 0.72
.;.;.;B;P;.;.;.;.
Vest4
0.14, 0.13, 0.17, 0.13, 0.15, 0.13
MutPred
0.28
.;.;.;.;Gain of solvent accessibility (P = 0.0584);.;Gain of solvent accessibility (P = 0.0584);.;.;
MVP
0.98
MPC
0.065
ClinPred
0.17
T
GERP RS
-0.89
Varity_R
0.036
gMVP
0.26

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: rs56305733; hg19: chr2-190719347; COSMIC: COSV100575446; COSMIC: COSV100575446; API