rs3117577

Positions:

• chr6-31759697-A-G

Variant summary

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

The NM_172166.4(MSH5):​c.1496-89A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.098 in 1,467,932 control chromosomes in the GnomAD database, including 9,161 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 0.069 (509 hom., cov: 32)
  • Exomes 𝑓: 0.10 (8652 hom.)
• Consequence: MSH5 NM_172166.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.561

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=-0.88).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.105 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MSH5	NM_172166.4	c.1496-89A>G		intron_variant		ENST00000375750.9	NP_751898.1
MSH5-SAPCD1	NR_037846.1	n.1675-89A>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MSH5	ENST00000375750.9	c.1496-89A>G		intron_variant		1	NM_172166.4	ENSP00000364903	A2

Frequencies

GnomAD3 genomes AF: 0.0695 AC: 10564 AN: 152052 Hom.: 509 Cov.: 32

Gnomad AFR AF: 0.0388

Gnomad AMI AF: 0.0691

Gnomad AMR AF: 0.0319

Gnomad ASJ AF: 0.0397

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.0792

Gnomad MID AF: 0.0190

Gnomad NFE AF: 0.108

Gnomad OTH AF: 0.0532

GnomAD4 exome AF: 0.101 AC: 133323 AN: 1315762 Hom.: 8652 Cov.: 20 AF XY: 0.0980 AC XY: 64243 AN XY: 655536

Gnomad4 AFR exome AF: 0.0411

Gnomad4 AMR exome AF: 0.0231

Gnomad4 ASJ exome AF: 0.0408

Gnomad4 EAS exome AF: 0.000103

Gnomad4 SAS exome AF: 0.000347

Gnomad4 FIN exome AF: 0.0816

Gnomad4 NFE exome AF: 0.121

Gnomad4 OTH exome AF: 0.0878

GnomAD4 genome AF: 0.0694 AC: 10562 AN: 152170 Hom.: 509 Cov.: 32 AF XY: 0.0646 AC XY: 4808 AN XY: 74406

Gnomad4 AFR AF: 0.0387

Gnomad4 AMR AF: 0.0318

Gnomad4 ASJ AF: 0.0397

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000207

Gnomad4 FIN AF: 0.0792

Gnomad4 NFE AF: 0.108

Gnomad4 OTH AF: 0.0526

Alfa AF: 0.0937 Hom.: 1220

Bravo AF: 0.0648

Asia WGS AF: 0.00635 AC: 23 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	11
DANN	Benign	0.68
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		0.95

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.060		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: rs3117577; hg19: chr6-31727474;