5-80824711-C-G

Position:

• chr5-80824711-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.2813+10970C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0807 in 152,256 control chromosomes in the GnomAD database, including 893 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 0.081 (893 hom., cov: 32)
• Consequence: MSH3 NM_002439.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.867

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=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.315 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MSH3	NM_002439.5	c.2813+10970C>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+10970C>G		intron_variant		1	NM_002439.5	ENSP00000265081	P2

Frequencies

GnomAD3 genomes AF: 0.0808 AC: 12287 AN: 152138 Hom.: 893 Cov.: 32

Gnomad AFR AF: 0.0273

Gnomad AMI AF: 0.0991

Gnomad AMR AF: 0.191

Gnomad ASJ AF: 0.110

Gnomad EAS AF: 0.329

Gnomad SAS AF: 0.0721

Gnomad FIN AF: 0.0697

Gnomad MID AF: 0.0443

Gnomad NFE AF: 0.0706

Gnomad OTH AF: 0.0774

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

GnomAD4 genome AF: 0.0807 AC: 12291 AN: 152256 Hom.: 893 Cov.: 32 AF XY: 0.0841 AC XY: 6260 AN XY: 74452

Gnomad4 AFR AF: 0.0272

Gnomad4 AMR AF: 0.191

Gnomad4 ASJ AF: 0.110

Gnomad4 EAS AF: 0.328

Gnomad4 SAS AF: 0.0724

Gnomad4 FIN AF: 0.0697

Gnomad4 NFE AF: 0.0706

Gnomad4 OTH AF: 0.0785

Alfa AF: 0.0812 Hom.: 96

Bravo AF: 0.0951

Asia WGS AF: 0.158 AC: 550 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.46
DANN	Benign	0.74

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: rs3797897; hg19: chr5-80120530;