rs10079641

Positions:

• chr5-80798145-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.2655+5301C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0788 in 152,026 control chromosomes in the GnomAD database, including 536 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 0.079 (536 hom., cov: 32)
• Consequence: MSH3 NM_002439.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.906

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 (NFE) allele frequency at 95% confidence interval = 0.0906 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MSH3	NM_002439.5	c.2655+5301C>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.2655+5301C>G		intron_variant		1	NM_002439.5	ENSP00000265081	P2
MSH3	ENST00000658259.1	c.2487+5301C>G		intron_variant				ENSP00000499617	A2
MSH3	ENST00000667069.1	c.2460+5301C>G		intron_variant				ENSP00000499502
MSH3	ENST00000670357.1	c.2655+5301C>G		intron_variant, NMD_transcript_variant				ENSP00000499791

Frequencies

GnomAD3 genomes AF: 0.0787 AC: 11956 AN: 151908 Hom.: 533 Cov.: 32

Gnomad AFR AF: 0.0676

Gnomad AMI AF: 0.221

Gnomad AMR AF: 0.0651

Gnomad ASJ AF: 0.0516

Gnomad EAS AF: 0.000772

Gnomad SAS AF: 0.0424

Gnomad FIN AF: 0.103

Gnomad MID AF: 0.0696

Gnomad NFE AF: 0.0926

Gnomad OTH AF: 0.0834

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

GnomAD4 genome AF: 0.0788 AC: 11986 AN: 152026 Hom.: 536 Cov.: 32 AF XY: 0.0780 AC XY: 5794 AN XY: 74288

Gnomad4 AFR AF: 0.0682

Gnomad4 AMR AF: 0.0649

Gnomad4 ASJ AF: 0.0516

Gnomad4 EAS AF: 0.000773

Gnomad4 SAS AF: 0.0420

Gnomad4 FIN AF: 0.103

Gnomad4 NFE AF: 0.0926

Gnomad4 OTH AF: 0.0849

Alfa AF: 0.0898 Hom.: 74

Bravo AF: 0.0752

Asia WGS AF: 0.0330 AC: 115 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	1.5
DANN	Benign	0.72

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: rs10079641; hg19: chr5-80093964;