5-80787812-G-A

Position:

• chr5-80787812-G-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_002439.5(MSH3):​c.2543+140G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.85 in 660,196 control chromosomes in the GnomAD database, including 239,146 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.85 (54469 hom., cov: 33)
  • Exomes 𝑓: 0.85 (184677 hom.)
• Consequence: MSH3 NM_002439.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.441

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BP6: Variant 5-80787812-G-A is Benign according to our data. Variant chr5-80787812-G-A is described in ClinVar as [Benign]. Clinvar id is 1251794.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.976 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MSH3	NM_002439.5	c.2543+140G>A		intron_variant		ENST00000265081.7	NP_002430.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MSH3	ENST00000265081.7	c.2543+140G>A		intron_variant		1	NM_002439.5	ENSP00000265081	P2
MSH3	ENST00000658259.1	c.2375+140G>A		intron_variant				ENSP00000499617	A2
MSH3	ENST00000667069.1	c.2348+140G>A		intron_variant				ENSP00000499502
MSH3	ENST00000670357.1	c.2543+140G>A		intron_variant, NMD_transcript_variant				ENSP00000499791

Frequencies

GnomAD3 genomes AF: 0.846 AC: 128652 AN: 152142 Hom.: 54420 Cov.: 33

Gnomad AFR AF: 0.839

Gnomad AMI AF: 0.839

Gnomad AMR AF: 0.859

Gnomad ASJ AF: 0.797

Gnomad EAS AF: 0.999

Gnomad SAS AF: 0.867

Gnomad FIN AF: 0.868

Gnomad MID AF: 0.788

Gnomad NFE AF: 0.833

Gnomad OTH AF: 0.836

GnomAD4 exome AF: 0.851 AC: 432374 AN: 507936 Hom.: 184677 AF XY: 0.851 AC XY: 233362 AN XY: 274088

Gnomad4 AFR exome AF: 0.838

Gnomad4 AMR exome AF: 0.892

Gnomad4 ASJ exome AF: 0.820

Gnomad4 EAS exome AF: 1.00

Gnomad4 SAS exome AF: 0.871

Gnomad4 FIN exome AF: 0.864

Gnomad4 NFE exome AF: 0.831

Gnomad4 OTH exome AF: 0.842

GnomAD4 genome AF: 0.846 AC: 128758 AN: 152260 Hom.: 54469 Cov.: 33 AF XY: 0.849 AC XY: 63192 AN XY: 74436

Gnomad4 AFR AF: 0.839

Gnomad4 AMR AF: 0.859

Gnomad4 ASJ AF: 0.797

Gnomad4 EAS AF: 0.999

Gnomad4 SAS AF: 0.867

Gnomad4 FIN AF: 0.868

Gnomad4 NFE AF: 0.833

Gnomad4 OTH AF: 0.838

Alfa AF: 0.835 Hom.: 24142

Bravo AF: 0.845

Asia WGS AF: 0.920 AC: 3199 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 22, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	5.2
DANN	Benign	0.52

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: rs33010; hg19: chr5-80083631;