rs408626

Positions:

• chr5-80655314-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.237+350T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.47 in 244,428 control chromosomes in the GnomAD database, including 27,625 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 0.47 (17054 hom., cov: 27)
  • Exomes 𝑓: 0.46 (10571 hom.)
• Consequence: MSH3 NM_002439.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.253

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]

MSH3 (HGNC:):

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 = 0.598 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MSH3	NM_002439.5	c.237+350T>C		intron_variant		ENST00000265081.7	NP_002430.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MSH3	ENST00000265081.7	c.237+350T>C		intron_variant		1	NM_002439.5	ENSP00000265081.6
MSH3	ENST00000658259.1	c.69+52T>C		intron_variant				ENSP00000499617.1
MSH3	ENST00000667069.1	c.237+350T>C		intron_variant				ENSP00000499502.1
MSH3	ENST00000670357.1	n.237+350T>C		intron_variant				ENSP00000499791.1

Frequencies

GnomAD3 genomes AF: 0.474 AC: 71154 AN: 150100 Hom.: 17046 Cov.: 27

Gnomad AFR AF: 0.546

Gnomad AMI AF: 0.534

Gnomad AMR AF: 0.497

Gnomad ASJ AF: 0.421

Gnomad EAS AF: 0.615

Gnomad SAS AF: 0.339

Gnomad FIN AF: 0.447

Gnomad MID AF: 0.421

Gnomad NFE AF: 0.432

Gnomad OTH AF: 0.446

GnomAD4 exome AF: 0.462 AC: 43554 AN: 94212 Hom.: 10571 Cov.: 0 AF XY: 0.458 AC XY: 20240 AN XY: 44186

Gnomad4 AFR exome AF: 0.538

Gnomad4 AMR exome AF: 0.514

Gnomad4 ASJ exome AF: 0.422

Gnomad4 EAS exome AF: 0.672

Gnomad4 SAS exome AF: 0.306

Gnomad4 FIN exome AF: 0.410

Gnomad4 NFE exome AF: 0.425

Gnomad4 OTH exome AF: 0.445

GnomAD4 genome AF: 0.474 AC: 71212 AN: 150216 Hom.: 17054 Cov.: 27 AF XY: 0.473 AC XY: 34651 AN XY: 73308

Gnomad4 AFR AF: 0.546

Gnomad4 AMR AF: 0.497

Gnomad4 ASJ AF: 0.421

Gnomad4 EAS AF: 0.615

Gnomad4 SAS AF: 0.338

Gnomad4 FIN AF: 0.447

Gnomad4 NFE AF: 0.432

Gnomad4 OTH AF: 0.447

Alfa AF: 0.453 Hom.: 1968

Bravo AF: 0.487

Asia WGS AF: 0.445 AC: 1543 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	9.8
DANN	Benign	0.67

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: rs408626; hg19: chr5-79951133; COSMIC: COSV54147333; COSMIC: COSV54147333;