Variant rs147084726 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_000534.5(PMS1):c.1001C>T(p.Thr334Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000444 in 1,593,580 control chromosomes in the GnomAD database, including 5 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as not provided (no stars).

Frequency

Genomes: 𝑓 0.00033 ( 1 hom., cov: 32)

Exomes 𝑓: 0.00046 ( 4 hom. )

Consequence

PMS1
NM_000534.5 missense

Scores

Clinical Significance

not provided no classification provided O:1

Conservation

PhyloP100: 0.228

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 -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.005335659).

BS2

High Homozygotes in GnomAdExome4 at 4 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PMS1	NM_000534.5 linkuse as main transcript	c.1001C>T	p.Thr334Met	missense_variant	9/13	ENST00000441310.7	NP_000525.1
LOC105373796	XR_001739151.2 linkuse as main transcript	n.319-1416G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PMS1	ENST00000441310.7 linkuse as main transcript	c.1001C>T	p.Thr334Met	missense_variant	9/13	1	NM_000534.5	ENSP00000406490	P1	P54277-1

Frequencies

GnomAD3 genomes

AF:

0.000335

AC:

AN:

152018

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000725

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000459

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00561

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00949

Gnomad NFE

AF:

0.000162

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000753

AC:

179

AN:

237596

Hom.:

AF XY:

0.00105

AC XY:

135

AN XY:

128612

show subpopulations

Gnomad AFR exome

AF:

0.0000662

Gnomad AMR exome

AF:

0.000188

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000565

Gnomad SAS exome

AF:

0.00500

Gnomad FIN exome

AF:

0.0000466

Gnomad NFE exome

AF:

0.000293

Gnomad OTH exome

AF:

0.000520

GnomAD4 exome

AF:

0.000456

AC:

657

AN:

1441444

Hom.:

Cov.:

AF XY:

0.000612

AC XY:

438

AN XY:

715756

show subpopulations

Gnomad4 AFR exome

AF:

0.0000304

Gnomad4 AMR exome

AF:

0.000236

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000508

Gnomad4 SAS exome

AF:

0.00515

Gnomad4 FIN exome

AF:

0.0000189

Gnomad4 NFE exome

AF:

0.000169

Gnomad4 OTH exome

AF:

0.000554

GnomAD4 genome

AF:

0.000329

AC:

AN:

152136

Hom.:

Cov.:

AF XY:

0.000457

AC XY:

AN XY:

74372

show subpopulations

Gnomad4 AFR

AF:

0.0000723

Gnomad4 AMR

AF:

0.000458

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00541

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000162

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000765

Hom.:

Bravo

AF:

0.000189

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.000519

AC:

ESP6500AA

AF:

0.000238

AC:

ESP6500EA

AF:

0.000117

AC:

ExAC

AF:

0.000942

AC:

114

Asia WGS

AF:

0.00173

AC:

AN:

3472

ClinVar

Significance: not provided

Submissions summary: Other:1

Revision: no classification provided

LINK: link

Submissions by phenotype

not specified

Other:1

not provided, no classification provided

reference population

ITMI

Sep 19, 2013

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.061

BayesDel_addAF

Benign

-0.38

BayesDel_noAF

Benign

-0.32

CADD

Benign

DANN

Benign

0.89

DEOGEN2

Benign

0.20

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

Eigen

Benign

-0.55

Eigen_PC

Benign

-0.50

FATHMM_MKL

Benign

0.062

LIST_S2

Benign

0.81

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

M_CAP

Benign

0.031

MetaRNN

Benign

0.0053

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

MetaSVM

Benign

-0.76

MutationAssessor

Benign

0.76

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

MutationTaster

Benign

1.0

N;N;N;N;N;N

PrimateAI

Benign

0.33

PROVEAN

Benign

-0.59

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

REVEL

Benign

0.23

Sift

Benign

0.18

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

Sift4G

Benign

0.20

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

Polyphen

0.64, 0.46

.;.;.;P;P;.;.;.;.

Vest4

0.096, 0.14, 0.090, 0.15, 0.091

MVP

0.88

MPC

0.079

ClinPred

0.011

GERP RS

0.90

Varity_R

0.014

gMVP

0.22

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

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