Variant rs707938 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.2148A>G(p.Gln716=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.353 in 1,613,718 control chromosomes in the GnomAD database, including 106,430 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.43 ( 15883 hom., cov: 33)

Exomes 𝑓: 0.34 ( 90547 hom. )

Consequence

MSH5
NM_172166.4 synonymous

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.419

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:):

MSH5-SAPCD1 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=-0.49).

BP6

Variant 6-31761582-A-G is Benign according to our data. Variant chr6-31761582-A-G is described in ClinVar as [Benign]. Clinvar id is 403112.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=0.419 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.641 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.2148A>G	p.Gln716=	synonymous_variant	22/25	ENST00000375750.9	NP_751898.1
MSH5-SAPCD1	NR_037846.1 linkuse as main transcript	n.2327A>G		non_coding_transcript_exon_variant	22/29

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MSH5	ENST00000375750.9 linkuse as main transcript	c.2148A>G	p.Gln716=	synonymous_variant	22/25	1	NM_172166.4	ENSP00000364903	A2	O43196-1

Frequencies

GnomAD3 genomes

AF:

0.433

AC:

65835

AN:

151992

Hom.:

15848

Cov.:

show subpopulations

Gnomad AFR

AF:

0.648

Gnomad AMI

AF:

0.263

Gnomad AMR

AF:

0.411

Gnomad ASJ

AF:

0.308

Gnomad EAS

AF:

0.347

Gnomad SAS

AF:

0.495

Gnomad FIN

AF:

0.446

Gnomad MID

AF:

0.392

Gnomad NFE

AF:

0.317

Gnomad OTH

AF:

0.427

GnomAD3 exomes

AF:

0.382

AC:

95769

AN:

250692

Hom.:

19610

AF XY:

0.379

AC XY:

51357

AN XY:

135678

show subpopulations

Gnomad AFR exome

AF:

0.653

Gnomad AMR exome

AF:

0.422

Gnomad ASJ exome

AF:

0.306

Gnomad EAS exome

AF:

0.335

Gnomad SAS exome

AF:

0.476

Gnomad FIN exome

AF:

0.427

Gnomad NFE exome

AF:

0.313

Gnomad OTH exome

AF:

0.361

GnomAD4 exome

AF:

0.344

AC:

503039

AN:

1461606

Hom.:

90547

Cov.:

AF XY:

0.346

AC XY:

251597

AN XY:

727108

show subpopulations

Gnomad4 AFR exome

AF:

0.652

Gnomad4 AMR exome

AF:

0.418

Gnomad4 ASJ exome

AF:

0.315

Gnomad4 EAS exome

AF:

0.379

Gnomad4 SAS exome

AF:

0.473

Gnomad4 FIN exome

AF:

0.427

Gnomad4 NFE exome

AF:

0.315

Gnomad4 OTH exome

AF:

0.375

GnomAD4 genome

AF:

0.433

AC:

65921

AN:

152112

Hom.:

15883

Cov.:

AF XY:

0.437

AC XY:

32523

AN XY:

74368

show subpopulations

Gnomad4 AFR

AF:

0.648

Gnomad4 AMR

AF:

0.412

Gnomad4 ASJ

AF:

0.308

Gnomad4 EAS

AF:

0.347

Gnomad4 SAS

AF:

0.495

Gnomad4 FIN

AF:

0.446

Gnomad4 NFE

AF:

0.317

Gnomad4 OTH

AF:

0.430

Alfa

AF:

0.334

Hom.:

18002

Bravo

AF:

0.437

Asia WGS

AF:

0.515

AC:

1787

AN:

3478

EpiCase

AF:

0.299

EpiControl

AF:

0.303

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

-0.49

CADD

Benign

9.4

DANN

Benign

0.77

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

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