rs7712332

Positions:

• chr5-80662016-A-G

Variant summary

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

The NM_002439.5(MSH3):​c.359-3127A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.338 in 152,024 control chromosomes in the GnomAD database, including 8,760 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 0.34 (8760 hom., cov: 32)
• Consequence: MSH3 NM_002439.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.57

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=-0.97).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.361 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MSH3	NM_002439.5	c.359-3127A>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.359-3127A>G		intron_variant		1	NM_002439.5	ENSP00000265081.6
MSH3	ENST00000658259.1	c.191-3127A>G		intron_variant				ENSP00000499617.1
MSH3	ENST00000667069.1	c.359-3127A>G		intron_variant				ENSP00000499502.1
MSH3	ENST00000670357.1	n.359-3127A>G		intron_variant				ENSP00000499791.1

Frequencies

GnomAD3 genomes AF: 0.338 AC: 51401 AN: 151906 Hom.: 8751 Cov.: 32

Gnomad AFR AF: 0.332

Gnomad AMI AF: 0.452

Gnomad AMR AF: 0.282

Gnomad ASJ AF: 0.279

Gnomad EAS AF: 0.276

Gnomad SAS AF: 0.224

Gnomad FIN AF: 0.370

Gnomad MID AF: 0.304

Gnomad NFE AF: 0.365

Gnomad OTH AF: 0.329

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

GnomAD4 genome AF: 0.338 AC: 51428 AN: 152024 Hom.: 8760 Cov.: 32 AF XY: 0.334 AC XY: 24822 AN XY: 74306

Gnomad4 AFR AF: 0.332

Gnomad4 AMR AF: 0.282

Gnomad4 ASJ AF: 0.279

Gnomad4 EAS AF: 0.277

Gnomad4 SAS AF: 0.224

Gnomad4 FIN AF: 0.370

Gnomad4 NFE AF: 0.365

Gnomad4 OTH AF: 0.327

Alfa AF: 0.346 Hom.: 7010

Bravo AF: 0.335

Asia WGS AF: 0.249 AC: 865 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.92
DANN	Benign	0.51

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: rs7712332; hg19: chr5-79957835; COSMIC: COSV54147354;