Variant rs3115672 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_StrongBP6_ModerateBP7BA1

The NM_172166.4(MSH5):c.1716C>T(p.Thr572Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.101 in 1,607,220 control chromosomes in the GnomAD database, including 10,302 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.077 ( 559 hom., cov: 32)

Exomes 𝑓: 0.10 ( 9743 hom. )

Consequence

MSH5
NM_172166.4 synonymous

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.0320

Variant links:

Genes affected

MSH5 (HGNC:7328): (mutS homolog 5) This gene encodes a member of the mutS family of proteins that are involved in DNA mismatch repair and meiotic recombination. This protein is similar to a Saccharomyces cerevisiae protein that participates in segregation fidelity and crossing-over events during meiosis. This protein plays a role in promoting ionizing radiation-induced apoptosis. This protein forms hetero-oligomers with another member of this family, mutS homolog 4. Polymorphisms in this gene have been linked to various human diseases, including IgA deficiency, common variable immunodeficiency, and premature ovarian failure. Alternative splicing results multiple transcript variants. Read-through transcription also exists between this gene and the downstream chromosome 6 open reading frame 26 (C6orf26) gene. [provided by RefSeq, Feb 2011]

MSH5 links:

MSH5-SAPCD1 (HGNC:41994): (MSH5-SAPCD1 readthrough (NMD candidate)) This locus represents naturally occurring read-through transcription between the neighboring mutS homolog 5 (MSH5) and chromosome 6 open reading frame 26 (C6orf26) genes. The read-through transcript is a candidate for nonsense-mediated mRNA decay (NMD), and is thus unlikely to produce a protein product. [provided by RefSeq, Feb 2011]

MSH5-SAPCD1 links:

MSH5 (HGNC:):

MSH5 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -15 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.53).

BP6

Variant 6-31760120-C-T is Benign according to our data. Variant chr6-31760120-C-T is described in ClinVar as [Benign]. Clinvar id is 403110.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=0.032 with no splicing effect.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.106 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MSH5	NM_172166.4 linkuse as main transcript	c.1716C>T	p.Thr572Thr	synonymous_variant	19/25	ENST00000375750.9	NP_751898.1	O43196-1A0A024RCM1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MSH5	ENST00000375750.9 linkuse as main transcript	c.1716C>T	p.Thr572Thr	synonymous_variant	19/25	1	NM_172166.4	ENSP00000364903.3		O43196-1
MSH5-SAPCD1	ENST00000493662.6 linkuse as main transcript	n.1767C>T		non_coding_transcript_exon_variant	19/29	1		ENSP00000417871.2		A0A024RCV8

Frequencies

GnomAD3 genomes

AF:

0.0766

AC:

11657

AN:

152128

Hom.:

559

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0627

Gnomad AMI

AF:

0.0691

Gnomad AMR

AF:

0.0372

Gnomad ASJ

AF:

0.0397

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00145

Gnomad FIN

AF:

0.0788

Gnomad MID

AF:

0.0222

Gnomad NFE

AF:

0.108

Gnomad OTH

AF:

0.0590

GnomAD3 exomes

AF:

0.0642

AC:

15692

AN:

244400

Hom.:

833

AF XY:

0.0625

AC XY:

8257

AN XY:

132034

show subpopulations

Gnomad AFR exome

AF:

0.0618

Gnomad AMR exome

AF:

0.0238

Gnomad ASJ exome

AF:

0.0384

Gnomad EAS exome

AF:

0.0000546

Gnomad SAS exome

AF:

0.00202

Gnomad FIN exome

AF:

0.0784

Gnomad NFE exome

AF:

0.103

Gnomad OTH exome

AF:

0.0636

GnomAD4 exome

AF:

0.104

AC:

151306

AN:

1454974

Hom.:

9743

Cov.:

AF XY:

0.100

AC XY:

72696

AN XY:

723488

show subpopulations

Gnomad4 AFR exome

AF:

0.0646

Gnomad4 AMR exome

AF:

0.0253

Gnomad4 ASJ exome

AF:

0.0408

Gnomad4 EAS exome

AF:

0.000101

Gnomad4 SAS exome

AF:

0.00268

Gnomad4 FIN exome

AF:

0.0808

Gnomad4 NFE exome

AF:

0.124

Gnomad4 OTH exome

AF:

0.0905

GnomAD4 genome

AF:

0.0766

AC:

11658

AN:

152246

Hom.:

559

Cov.:

AF XY:

0.0712

AC XY:

5296

AN XY:

74430

show subpopulations

Gnomad4 AFR

AF:

0.0626

Gnomad4 AMR

AF:

0.0371

Gnomad4 ASJ

AF:

0.0397

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00145

Gnomad4 FIN

AF:

0.0788

Gnomad4 NFE

AF:

0.108

Gnomad4 OTH

AF:

0.0583

Alfa

AF:

0.0917

Hom.:

951

Bravo

AF:

0.0733

Asia WGS

AF:

0.00837

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Mar 29, 2016

Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Frequency -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.53

CADD

Benign

DANN

Benign

0.85

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.15

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