rs1428030

chr5-80712885-T-C

Variant summary

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

The NM_002439.5(MSH3):c.1341-12568T>C 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 152,056 control chromosomes in the GnomAD database, including 1,693 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 (1693 hom., cov: 32)
• Consequence: MSH3 NM_002439.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.14

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=-0.82).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.317 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MSH3	NM_002439.5	c.1341-12568T>C		intron_variant		ENST00000265081.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MSH3	ENST00000265081.7	c.1341-12568T>C		intron_variant		1	NM_002439.5	P2
MSH3	ENST00000658259.1	c.1173-12568T>C		intron_variant				A2
MSH3	ENST00000667069.1	c.1341-12568T>C		intron_variant
MSH3	ENST00000670357.1	c.1341-12568T>C		intron_variant, NMD_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.126 AC: 19088 AN: 151938 Hom.: 1689 Cov.: 32

Gnomad AFR AF: 0.198

Gnomad AMI AF: 0.0826

Gnomad AMR AF: 0.213

Gnomad ASJ AF: 0.130

Gnomad EAS AF: 0.331

Gnomad SAS AF: 0.0795

Gnomad FIN AF: 0.0649

Gnomad MID AF: 0.0728

Gnomad NFE AF: 0.0601

Gnomad OTH AF: 0.116

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

GnomAD4 genome AF: 0.126 AC: 19113 AN: 152056 Hom.: 1693 Cov.: 32 AF XY: 0.128 AC XY: 9497 AN XY: 74314

Gnomad4 AFR AF: 0.198

Gnomad4 AMR AF: 0.213

Gnomad4 ASJ AF: 0.130

Gnomad4 EAS AF: 0.330

Gnomad4 SAS AF: 0.0797

Gnomad4 FIN AF: 0.0649

Gnomad4 NFE AF: 0.0601

Gnomad4 OTH AF: 0.116

Alfa AF: 0.0797 Hom.: 818

Bravo AF: 0.147

Asia WGS AF: 0.177 AC: 612 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
Cadd	Benign	12
Dann	Benign	0.77

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: rs1428030; hg19: chr5-80008704;