NM_172166.4:c.812+2483A>G

Variant names:

• chr6-31749915-A-G
• rs3117572
• NM_172166.4:c.812+2483A>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+2483A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.876 in 152,200 control chromosomes in the GnomAD database, including 58,747 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 0.88 (58747 hom., cov: 32)
• Consequence: MSH5 NM_172166.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.22
• Publications: 37 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=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.958 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MSH5	NM_172166.4	MANE Select	c.812+2483A>G		intron	N/A	NP_751898.1	O43196-1
	MSH5	NM_172165.4		c.812+2483A>G		intron	N/A	NP_751897.1	O43196-2
	MSH5	NM_002441.5		c.812+2483A>G		intron	N/A	NP_002432.1	A0A024RCM1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MSH5	ENST00000375750.9	TSL:1 MANE Select	c.812+2483A>G		intron	N/A	ENSP00000364903.3	O43196-1
	MSH5	ENST00000375703.7	TSL:1	c.812+2483A>G		intron	N/A	ENSP00000364855.3	O43196-2
	MSH5	ENST00000375755.8	TSL:1	c.812+2483A>G		intron	N/A	ENSP00000364908.3	O43196-1

Frequencies

GnomAD3 genomes AF: 0.876 AC: 133231 AN: 152082 Hom.: 58689 Cov.: 32

Gnomad AFR AF: 0.966

Gnomad AMI AF: 0.768

Gnomad AMR AF: 0.909

Gnomad ASJ AF: 0.934

Gnomad EAS AF: 0.785

Gnomad SAS AF: 0.893

Gnomad FIN AF: 0.845

Gnomad MID AF: 0.943

Gnomad NFE AF: 0.822

Gnomad OTH AF: 0.901

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

GnomAD4 genome AF: 0.876 AC: 133349 AN: 152200 Hom.: 58747 Cov.: 32 AF XY: 0.877 AC XY: 65231 AN XY: 74390

African (AFR) AF: 0.966 AC: 40126 AN: 41528

American (AMR) AF: 0.910 AC: 13902 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.934 AC: 3242 AN: 3472

East Asian (EAS) AF: 0.785 AC: 4070 AN: 5182

South Asian (SAS) AF: 0.894 AC: 4308 AN: 4818

European-Finnish (FIN) AF: 0.845 AC: 8942 AN: 10588

Middle Eastern (MID) AF: 0.939 AC: 276 AN: 294

European-Non Finnish (NFE) AF: 0.822 AC: 55881 AN: 68010

Other (OTH) AF: 0.901 AC: 1902 AN: 2112

Alfa AF: 0.847 Hom.: 215087

Bravo AF: 0.885

Asia WGS AF: 0.892 AC: 3105 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.16
DANN	Benign	0.40
PhyloP100		-2.2
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: rs3117572; hg19: chr6-31717692;