5-80869595-C-G

Position:

• chr5-80869595-C-G

Variant summary

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

The NM_002439.5(MSH3):​c.3131-3521C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.126 in 151,778 control chromosomes in the GnomAD database, including 1,561 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 0.13 (1561 hom., cov: 30)
• Consequence: MSH3 NM_002439.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.132

Genes affected

MSH3 (HGNC:7326): (mutS homolog 3) The protein encoded by this gene forms a heterodimer with MSH2 to form MutS beta, part of the post-replicative DNA mismatch repair system. MutS beta initiates mismatch repair by binding to a mismatch and then forming a complex with MutL alpha heterodimer. This gene contains a polymorphic 9 bp tandem repeat sequence in the first exon. The repeat is present 6 times in the reference genome sequence and 3-7 repeats have been reported. Defects in this gene are a cause of susceptibility to endometrial cancer. [provided by RefSeq, Mar 2011]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.339 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MSH3	NM_002439.5	c.3131-3521C>G		intron_variant		ENST00000265081.7	NP_002430.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MSH3	ENST00000265081.7	c.3131-3521C>G		intron_variant		1	NM_002439.5	ENSP00000265081	P2

Frequencies

GnomAD3 genomes AF: 0.126 AC: 19121 AN: 151664 Hom.: 1560 Cov.: 30

Gnomad AFR AF: 0.161

Gnomad AMI AF: 0.100

Gnomad AMR AF: 0.214

Gnomad ASJ AF: 0.152

Gnomad EAS AF: 0.353

Gnomad SAS AF: 0.116

Gnomad FIN AF: 0.0707

Gnomad MID AF: 0.0732

Gnomad NFE AF: 0.0766

Gnomad OTH AF: 0.120

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

GnomAD4 genome AF: 0.126 AC: 19138 AN: 151778 Hom.: 1561 Cov.: 30 AF XY: 0.128 AC XY: 9516 AN XY: 74154

Gnomad4 AFR AF: 0.161

Gnomad4 AMR AF: 0.214

Gnomad4 ASJ AF: 0.152

Gnomad4 EAS AF: 0.352

Gnomad4 SAS AF: 0.116

Gnomad4 FIN AF: 0.0707

Gnomad4 NFE AF: 0.0766

Gnomad4 OTH AF: 0.121

Alfa AF: 0.110 Hom.: 146

Bravo AF: 0.147

Asia WGS AF: 0.196 AC: 682 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	9.3
DANN	Benign	0.61

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: rs4703819; hg19: chr5-80165414;