rs707915

chr6-31743191-T-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.50

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-SAPCD1 (HGNC:):

ACMG classification

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	UniProt
MSH5	NM_172166.4	c.415+21T>A		intron_variant		ENST00000375750.9
MSH5-SAPCD1	NR_037846.1	n.543+21T>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MSH5	ENST00000375750.9	c.415+21T>A		intron_variant		1	NM_172166.4	A2

Frequencies

GnomAD3 genomes AF: 0.108 AC: 16386 AN: 151998 Hom.: 1205 Cov.: 31

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

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.: 30 AF XY: 0.0679 AC XY: 49321 AN XY: 725870

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.: 31 AF XY: 0.107 AC XY: 7971 AN XY: 74366

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	13
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

Other links and lift over

dbSNP: rs707915; hg19: chr6-31710968;