Variant 2-189795810-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_StrongBP6_ModerateBP7BS2

The NM_000534.5(PMS1):c.174G>T(p.Gly58=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00369 in 1,613,812 control chromosomes in the GnomAD database, including 18 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0025 ( 3 hom., cov: 32)

Exomes 𝑓: 0.0038 ( 15 hom. )

Consequence

PMS1
NM_000534.5 synonymous

Scores

Clinical Significance

Benign criteria provided, single submitter B:2

Conservation

PhyloP100: -0.0310

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -11 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.61).

BP6

Variant 2-189795810-G-T is Benign according to our data. Variant chr2-189795810-G-T is described in ClinVar as [Benign]. Clinvar id is 333202.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=-0.031 with no splicing effect.

BS2

High Homozygotes in GnomAd4 at 3 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PMS1	NM_000534.5 linkuse as main transcript	c.174G>T	p.Gly58=	synonymous_variant	3/13	ENST00000441310.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PMS1	ENST00000441310.7 linkuse as main transcript	c.174G>T	p.Gly58=	synonymous_variant	3/13	1	NM_000534.5	P1	P54277-1

Frequencies

GnomAD3 genomes

AF:

0.00249

AC:

379

AN:

152174

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00106

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000327

Gnomad ASJ

AF:

0.00144

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000828

Gnomad FIN

AF:

0.000566

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00457

Gnomad OTH

AF:

0.00191

GnomAD3 exomes

AF:

0.00274

AC:

690

AN:

251422

Hom.:

AF XY:

0.00280

AC XY:

380

AN XY:

135890

show subpopulations

Gnomad AFR exome

AF:

0.000677

Gnomad AMR exome

AF:

0.000896

Gnomad ASJ exome

AF:

0.00298

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00160

Gnomad FIN exome

AF:

0.000739

Gnomad NFE exome

AF:

0.00466

Gnomad OTH exome

AF:

0.00375

GnomAD4 exome

AF:

0.00382

AC:

5584

AN:

1461520

Hom.:

Cov.:

AF XY:

0.00381

AC XY:

2767

AN XY:

727090

show subpopulations

Gnomad4 AFR exome

AF:

0.000448

Gnomad4 AMR exome

AF:

0.000961

Gnomad4 ASJ exome

AF:

0.00241

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.00147

Gnomad4 FIN exome

AF:

0.00152

Gnomad4 NFE exome

AF:

0.00459

Gnomad4 OTH exome

AF:

0.00242

GnomAD4 genome

AF:

0.00249

AC:

379

AN:

152292

Hom.:

Cov.:

AF XY:

0.00240

AC XY:

179

AN XY:

74472

show subpopulations

Gnomad4 AFR

AF:

0.00106

Gnomad4 AMR

AF:

0.000327

Gnomad4 ASJ

AF:

0.00144

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000829

Gnomad4 FIN

AF:

0.000566

Gnomad4 NFE

AF:

0.00457

Gnomad4 OTH

AF:

0.00189

Alfa

AF:

0.00252

Hom.:

Bravo

AF:

0.00243

Asia WGS

AF:

0.000577

AC:

AN:

3478

EpiCase

AF:

0.00311

EpiControl

AF:

0.00308

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Dec 31, 2019

- -

PMS1-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Sep 29, 2020

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.61

CADD

Benign

6.0

DANN

Benign

0.60

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.

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