5-80830334-A-G

Position:

• chr5-80830334-A-G

Variant summary

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

The ENST00000265081.7(MSH3):​c.2813+16593A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.202 in 152,054 control chromosomes in the GnomAD database, including 3,441 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 0.20 (3441 hom., cov: 32)
• Consequence: MSH3 ENST00000265081.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.15

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=-0.9).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.344 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MSH3	NM_002439.5	c.2813+16593A>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.2813+16593A>G		intron_variant		1	NM_002439.5	ENSP00000265081	P2

Frequencies

GnomAD3 genomes AF: 0.202 AC: 30705 AN: 151936 Hom.: 3440 Cov.: 32

Gnomad AFR AF: 0.122

Gnomad AMI AF: 0.382

Gnomad AMR AF: 0.166

Gnomad ASJ AF: 0.188

Gnomad EAS AF: 0.0948

Gnomad SAS AF: 0.358

Gnomad FIN AF: 0.258

Gnomad MID AF: 0.218

Gnomad NFE AF: 0.246

Gnomad OTH AF: 0.200

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

GnomAD4 genome AF: 0.202 AC: 30714 AN: 152054 Hom.: 3441 Cov.: 32 AF XY: 0.204 AC XY: 15137 AN XY: 74342

Gnomad4 AFR AF: 0.122

Gnomad4 AMR AF: 0.166

Gnomad4 ASJ AF: 0.188

Gnomad4 EAS AF: 0.0950

Gnomad4 SAS AF: 0.358

Gnomad4 FIN AF: 0.258

Gnomad4 NFE AF: 0.246

Gnomad4 OTH AF: 0.200

Alfa AF: 0.239 Hom.: 2095

Bravo AF: 0.184

Asia WGS AF: 0.225 AC: 784 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.22
DANN	Benign	0.60

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: rs249633; hg19: chr5-80126153;