Variant 2-189818173-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3

The NM_000534.5(PMS1):c.575A>G(p.His192Arg) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000701 in 1,426,622 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as not provided (no stars).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 7.0e-7 ( 0 hom. )

Consequence

PMS1
NM_000534.5 missense

Scores

Clinical Significance

not provided no classification provided O:1

Conservation

PhyloP100: 8.18

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 Uncertain_significance. Variant got 3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.829

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PMS1	NM_000534.5 linkuse as main transcript	c.575A>G	p.His192Arg	missense_variant	5/13	ENST00000441310.7	NP_000525.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PMS1	ENST00000441310.7 linkuse as main transcript	c.575A>G	p.His192Arg	missense_variant	5/13	1	NM_000534.5	ENSP00000406490	P1	P54277-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

7.01e-7

AC:

AN:

1426622

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

711786

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000117

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

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

Pathogenic

0.84

BayesDel_addAF

Pathogenic

0.32

BayesDel_noAF

Pathogenic

0.22

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.12

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

Eigen

Pathogenic

0.82

Eigen_PC

Pathogenic

0.76

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Uncertain

0.87

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

M_CAP

Uncertain

0.12

MetaRNN

Pathogenic

0.83

D;D;D;D;D;D;D;D;D;D;D

MetaSVM

Uncertain

0.65

MutationAssessor

Uncertain

2.9

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

MutationTaster

Benign

1.0

D;D;D;D;D;D

PrimateAI

Uncertain

0.62

PROVEAN

Pathogenic

-6.2

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

REVEL

Pathogenic

0.82

Sift

Uncertain

0.0040

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

Sift4G

Uncertain

0.0040

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

Polyphen

1.0, 0.99, 0.99

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

Vest4

0.88, 0.88, 0.85, 0.81, 0.80, 0.84, 0.86

MutPred

0.52

Gain of MoRF binding (P = 0.0234);.;.;Gain of MoRF binding (P = 0.0234);Gain of MoRF binding (P = 0.0234);Gain of MoRF binding (P = 0.0234);Gain of MoRF binding (P = 0.0234);Gain of MoRF binding (P = 0.0234);Gain of MoRF binding (P = 0.0234);.;.;

MVP

0.98

MPC

0.41

ClinPred

0.99

GERP RS

5.4

Varity_R

0.77

gMVP

0.67

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.31

Details are displayed if max score is > 0.2

DS_DG_spliceai

0.31

Position offset: -5

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