rs707939

chr6-31758911-C-A

Variant summary

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

The NM_172166.4(MSH5):c.1326+36C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.328 in 1,564,132 control chromosomes in the GnomAD database, including 89,118 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 0.27 (6781 hom., cov: 32)
  • Exomes 𝑓: 0.33 (82337 hom.)
• Consequence: MSH5 NM_172166.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.42

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=-0.82).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.349 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MSH5	NM_172166.4	c.1326+36C>A		intron_variant		ENST00000375750.9
MSH5-SAPCD1	NR_037846.1	n.1505+36C>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MSH5	ENST00000375750.9	c.1326+36C>A		intron_variant		1	NM_172166.4	A2

Frequencies

GnomAD3 genomes AF: 0.266 AC: 40373 AN: 151934 Hom.: 6778 Cov.: 32

Gnomad AFR AF: 0.0609

Gnomad AMI AF: 0.411

Gnomad AMR AF: 0.323

Gnomad ASJ AF: 0.514

Gnomad EAS AF: 0.362

Gnomad SAS AF: 0.312

Gnomad FIN AF: 0.304

Gnomad MID AF: 0.405

Gnomad NFE AF: 0.345

Gnomad OTH AF: 0.287

GnomAD3 exomes AF: 0.343 AC: 85522 AN: 249332 Hom.: 15751 AF XY: 0.347 AC XY: 46813 AN XY: 134770

Gnomad AFR exome AF: 0.0532

Gnomad AMR exome AF: 0.394

Gnomad ASJ exome AF: 0.521

Gnomad EAS exome AF: 0.368

Gnomad SAS exome AF: 0.318

Gnomad FIN exome AF: 0.310

Gnomad NFE exome AF: 0.362

Gnomad OTH exome AF: 0.352

GnomAD4 exome AF: 0.335 AC: 472721 AN: 1412080 Hom.: 82337 Cov.: 24 AF XY: 0.338 AC XY: 238182 AN XY: 705398

Gnomad4 AFR exome AF: 0.0490

Gnomad4 AMR exome AF: 0.387

Gnomad4 ASJ exome AF: 0.508

Gnomad4 EAS exome AF: 0.431

Gnomad4 SAS exome AF: 0.317

Gnomad4 FIN exome AF: 0.303

Gnomad4 NFE exome AF: 0.337

Gnomad4 OTH exome AF: 0.319

GnomAD4 genome AF: 0.266 AC: 40379 AN: 152052 Hom.: 6781 Cov.: 32 AF XY: 0.267 AC XY: 19842 AN XY: 74314

Gnomad4 AFR AF: 0.0608

Gnomad4 AMR AF: 0.323

Gnomad4 ASJ AF: 0.514

Gnomad4 EAS AF: 0.362

Gnomad4 SAS AF: 0.313

Gnomad4 FIN AF: 0.304

Gnomad4 NFE AF: 0.345

Gnomad4 OTH AF: 0.286

Alfa AF: 0.358 Hom.: 21778

Bravo AF: 0.259

Asia WGS AF: 0.305 AC: 1065 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
Cadd	Benign	0.31
Dann	Benign	0.74

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

Other links and lift over

dbSNP: rs707939; hg19: chr6-31726688; COSMIC: COSV65212319; COSMIC: COSV65212319;