6-31749919-A-G

Variant names:

• chr6-31749919-A-G
• rs1150793
• NM_172166.4:c.812+2487A>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 39 publications found

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:41994): (MSH5-SAPCD1 readthrough (NMD candidate)) This locus represents naturally occurring read-through transcription between the neighboring mutS homolog 5 (MSH5) and chromosome 6 open reading frame 26 (C6orf26) genes. The read-through transcript is a candidate for nonsense-mediated mRNA decay (NMD), and is thus unlikely to produce a protein product. [provided by RefSeq, Feb 2011]

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_172166.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MSH5	NM_172166.4	MANE Select	c.812+2487A>G		intron	N/A	NP_751898.1
	MSH5	NM_172165.4		c.812+2487A>G		intron	N/A	NP_751897.1
	MSH5	NM_002441.5		c.812+2487A>G		intron	N/A	NP_002432.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MSH5	ENST00000375750.9	TSL:1 MANE Select	c.812+2487A>G		intron	N/A	ENSP00000364903.3
	MSH5	ENST00000375703.7	TSL:1	c.812+2487A>G		intron	N/A	ENSP00000364855.3
	MSH5	ENST00000375755.8	TSL:1	c.812+2487A>G		intron	N/A	ENSP00000364908.3

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

African (AFR) AF: 0.204 AC: 8449 AN: 41508

American (AMR) AF: 0.0697 AC: 1066 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.0524 AC: 182 AN: 3470

East Asian (EAS) AF: 0.0753 AC: 391 AN: 5190

South Asian (SAS) AF: 0.116 AC: 560 AN: 4816

European-Finnish (FIN) AF: 0.0703 AC: 746 AN: 10608

Middle Eastern (MID) AF: 0.109 AC: 32 AN: 294

European-Non Finnish (NFE) AF: 0.0696 AC: 4737 AN: 68022

Other (OTH) AF: 0.106 AC: 224 AN: 2110

Alfa AF: 0.0851 Hom.: 1663

Bravo AF: 0.113

Asia WGS AF: 0.0840 AC: 292 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	1.2
DANN	Benign	0.71
PhyloP100		-0.29
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs1150793; hg19: chr6-31717696;