rs1150793

Positions:

• chr6-31749919-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.812+2487A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.108 in 152,220 control chromosomes in the GnomAD database, including 1,206 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 (1206 hom., cov: 32)
• Consequence: MSH5 NM_172166.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.289

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=-0.83).
• 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	c.812+2487A>G		intron_variant		ENST00000375750.9	NP_751898.1
MSH5-SAPCD1	NR_037846.1	n.991+2487A>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MSH5	ENST00000375750.9	c.812+2487A>G		intron_variant		1	NM_172166.4	ENSP00000364903	A2

Frequencies

GnomAD3 genomes AF: 0.108 AC: 16431 AN: 152102 Hom.: 1207 Cov.: 32

Gnomad AFR AF: 0.204

Gnomad AMI AF: 0.0493

Gnomad AMR AF: 0.0699

Gnomad ASJ AF: 0.0524

Gnomad EAS AF: 0.0748

Gnomad SAS AF: 0.117

Gnomad FIN AF: 0.0703

Gnomad MID AF: 0.111

Gnomad NFE AF: 0.0696

Gnomad OTH AF: 0.107

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.108 AC: 16432 AN: 152220 Hom.: 1206 Cov.: 32 AF XY: 0.107 AC XY: 7996 AN XY: 74436

Gnomad4 AFR AF: 0.204

Gnomad4 AMR AF: 0.0697

Gnomad4 ASJ AF: 0.0524

Gnomad4 EAS AF: 0.0753

Gnomad4 SAS AF: 0.116

Gnomad4 FIN AF: 0.0703

Gnomad4 NFE AF: 0.0696

Gnomad4 OTH AF: 0.106

Alfa AF: 0.0863 Hom.: 262

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	-0.83
CADD	Benign	1.2
DANN	Benign	0.71

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: rs1150793; hg19: chr6-31717696;