rs11964779

Positions:

• chr6-31743847-A-C

Variant summary

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

The ENST00000375750.9(MSH5):​c.416-57A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00678 in 1,591,922 control chromosomes in the GnomAD database, including 338 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 0.027 (161 hom., cov: 31)
  • Exomes 𝑓: 0.0046 (177 hom.)
• Consequence: MSH5 ENST00000375750.9 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.668

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=-0.65).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0831 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MSH5	NM_172166.4	c.416-57A>C		intron_variant		ENST00000375750.9	NP_751898.1
MSH5-SAPCD1	NR_037846.1	n.544-57A>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MSH5	ENST00000375750.9	c.416-57A>C		intron_variant		1	NM_172166.4	ENSP00000364903	A2

Frequencies

GnomAD3 genomes AF: 0.0271 AC: 4123 AN: 152090 Hom.: 162 Cov.: 31

Gnomad AFR AF: 0.0857

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0196

Gnomad ASJ AF: 0.00173

Gnomad EAS AF: 0.00347

Gnomad SAS AF: 0.00540

Gnomad FIN AF: 0.000377

Gnomad MID AF: 0.0253

Gnomad NFE AF: 0.00240

Gnomad OTH AF: 0.0263

GnomAD4 exome AF: 0.00463 AC: 6667 AN: 1439714 Hom.: 177 AF XY: 0.00422 AC XY: 3014 AN XY: 715046

Gnomad4 AFR exome AF: 0.0886

Gnomad4 AMR exome AF: 0.0233

Gnomad4 ASJ exome AF: 0.000887

Gnomad4 EAS exome AF: 0.00692

Gnomad4 SAS exome AF: 0.00173

Gnomad4 FIN exome AF: 0.000252

Gnomad4 NFE exome AF: 0.00155

Gnomad4 OTH exome AF: 0.00970

GnomAD4 genome AF: 0.0271 AC: 4124 AN: 152208 Hom.: 161 Cov.: 31 AF XY: 0.0267 AC XY: 1987 AN XY: 74424

Gnomad4 AFR AF: 0.0855

Gnomad4 AMR AF: 0.0195

Gnomad4 ASJ AF: 0.00173

Gnomad4 EAS AF: 0.00347

Gnomad4 SAS AF: 0.00540

Gnomad4 FIN AF: 0.000377

Gnomad4 NFE AF: 0.00240

Gnomad4 OTH AF: 0.0260

Alfa AF: 0.00706 Hom.: 37

Bravo AF: 0.0313

Asia WGS AF: 0.00606 AC: 22 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.65
CADD	Benign	2.5
DANN	Benign	0.87

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: rs11964779; hg19: chr6-31711624;