rs2066456

Variant names:

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 2P and 12B. PM2BP4_StrongBP6_Very_Strong

The NM_000534.5(PMS1):c.1895A>G(p.Asn632Ser) variant causes a missense change. The variant allele was found at a frequency of 0.000324 in 1,608,090 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 (★★). Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in UniProt.

Frequency

Genomes: 𝑓 0.0017 ( 0 hom., cov: 30)

Exomes 𝑓: 0.00018 ( 0 hom. )

Consequence

PMS1
NM_000534.5 missense

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:2O:1

Conservation

PhyloP100: 5.20

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]

PMS1 links:

LOC105373796 (HGNC:):

LOC105373796 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.005708903).

BP6

Variant 2-189863781-A-G is Benign according to our data. Variant chr2-189863781-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 135058.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PMS1	NM_000534.5 link	c.1895A>G	p.Asn632Ser	missense_variant	Exon 10 of 13	ENST00000441310.7	NP_000525.1	P54277-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PMS1	ENST00000441310.7 link	c.1895A>G	p.Asn632Ser	missense_variant	Exon 10 of 13	1	NM_000534.5	ENSP00000406490.3		P54277-1

Frequencies

GnomAD3 genomes

AF:

0.00169

AC:

257

AN:

152188

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00587

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000327

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000118

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.000412

AC:

103

AN:

250258

Hom.:

AF XY:

0.000251

AC XY:

AN XY:

135462

show subpopulations

Gnomad AFR exome

AF:

0.00531

Gnomad AMR exome

AF:

0.000290

Gnomad ASJ exome

AF:

0.0000995

Gnomad EAS exome

AF:

0.0000544

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000443

Gnomad OTH exome

AF:

0.000164

GnomAD4 exome

AF:

0.000181

AC:

263

AN:

1455784

Hom.:

Cov.:

AF XY:

0.000153

AC XY:

111

AN XY:

724710

show subpopulations

Gnomad4 AFR exome

AF:

0.00588

Gnomad4 AMR exome

AF:

0.000403

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000271

Gnomad4 OTH exome

AF:

0.000249

GnomAD4 genome

AF:

0.00169

AC:

258

AN:

152306

Hom.:

Cov.:

AF XY:

0.00165

AC XY:

123

AN XY:

74468

show subpopulations

Gnomad4 AFR

AF:

0.00587

Gnomad4 AMR

AF:

0.000327

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000118

Gnomad4 OTH

AF:

0.000473

Alfa

AF:

0.000429

Hom.:

Bravo

AF:

0.00178

ESP6500AA

AF:

0.00409

AC:

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.000544

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

EpiCase

AF:

0.00

EpiControl

AF:

0.0000593

ClinVar

Significance: Likely benign

Submissions summary: Benign:2Other:1

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1Other:1

Mar 06, 2020

Genetic Services Laboratory, University of Chicago

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Sep 19, 2013

ITMI

Significance: not provided

Review Status: no classification provided

Collection Method: reference population

- -

not provided

Benign:1

Oct 16, 2017

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.094

BayesDel_addAF

Benign

-0.19

BayesDel_noAF

Uncertain

-0.050

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.48

T;T;T;D;T;.;.;T

Eigen

Uncertain

0.24

Eigen_PC

Uncertain

0.36

FATHMM_MKL

Pathogenic

0.97

LIST_S2

Benign

0.85

D;.;D;D;D;T;T;D

M_CAP

Benign

0.084

MetaRNN

Benign

0.0057

T;T;T;T;T;T;T;T

MetaSVM

Pathogenic

0.92

MutationAssessor

Uncertain

2.0

.;.;.;.;M;.;.;.

PrimateAI

Benign

0.44

PROVEAN

Benign

-1.3

.;.;N;.;N;N;N;N

REVEL

Benign

0.059

Sift

Uncertain

0.015

.;.;D;.;D;D;D;D

Sift4G

Benign

0.14

.;T;T;T;T;T;T;T

Polyphen

0.25, 0.28

.;.;.;B;B;.;.;.

Vest4

0.19, 0.19, 0.20, 0.21, 0.25

MVP

0.99

MPC

0.095

ClinPred

0.020

GERP RS

5.5

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.17

gMVP

0.084

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over