Variant chr6-31743191-T-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_172166.4(MSH5):c.415+21T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0712 in 1,610,994 control chromosomes in the GnomAD database, including 5,250 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.11 ( 1204 hom., cov: 31)

Exomes 𝑓: 0.067 ( 4046 hom. )

Consequence

MSH5
NM_172166.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.50

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.73).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.2 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.415+21T>A		intron_variant		ENST00000375750.9	NP_751898.1
MSH5-SAPCD1	NR_037846.1 linkuse as main transcript	n.543+21T>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MSH5	ENST00000375750.9 linkuse as main transcript	c.415+21T>A		intron_variant		1	NM_172166.4	ENSP00000364903	A2	O43196-1

Frequencies

GnomAD3 genomes

AF:

0.108

AC:

16386

AN:

151998

Hom.:

1205

Cov.:

show subpopulations

Gnomad AFR

AF:

0.204

Gnomad AMI

AF:

0.0495

Gnomad AMR

AF:

0.0700

Gnomad ASJ

AF:

0.0524

Gnomad EAS

AF:

0.0746

Gnomad SAS

AF:

0.117

Gnomad FIN

AF:

0.0684

Gnomad MID

AF:

0.111

Gnomad NFE

AF:

0.0694

Gnomad OTH

AF:

0.107

GnomAD3 exomes

AF:

0.0799

AC:

19697

AN:

246490

Hom.:

1023

AF XY:

0.0798

AC XY:

10710

AN XY:

134282

show subpopulations

Gnomad AFR exome

AF:

0.210

Gnomad AMR exome

AF:

0.0527

Gnomad ASJ exome

AF:

0.0559

Gnomad EAS exome

AF:

0.0937

Gnomad SAS exome

AF:

0.0999

Gnomad FIN exome

AF:

0.0684

Gnomad NFE exome

AF:

0.0676

Gnomad OTH exome

AF:

0.0732

GnomAD4 exome

AF:

0.0674

AC:

98278

AN:

1458878

Hom.:

4046

Cov.:

AF XY:

0.0679

AC XY:

49321

AN XY:

725870

show subpopulations

Gnomad4 AFR exome

AF:

0.215

Gnomad4 AMR exome

AF:

0.0561

Gnomad4 ASJ exome

AF:

0.0547

Gnomad4 EAS exome

AF:

0.0450

Gnomad4 SAS exome

AF:

0.105

Gnomad4 FIN exome

AF:

0.0671

Gnomad4 NFE exome

AF:

0.0614

Gnomad4 OTH exome

AF:

0.0703

GnomAD4 genome

AF:

0.108

AC:

16387

AN:

152116

Hom.:

1204

Cov.:

AF XY:

0.107

AC XY:

7971

AN XY:

74366

show subpopulations

Gnomad4 AFR

AF:

0.204

Gnomad4 AMR

AF:

0.0698

Gnomad4 ASJ

AF:

0.0524

Gnomad4 EAS

AF:

0.0752

Gnomad4 SAS

AF:

0.116

Gnomad4 FIN

AF:

0.0684

Gnomad4 NFE

AF:

0.0695

Gnomad4 OTH

AF:

0.106

Alfa

AF:

0.0750

Hom.:

308

Bravo

AF:

0.113

Asia WGS

AF:

0.0840

AC:

292

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.73

CADD

Benign

DANN

Benign

0.85

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.10

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over