Variant 5-80656607-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_002439.5(MSH3):c.358+76G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.261 in 1,586,528 control chromosomes in the GnomAD database, including 56,530 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.26 ( 5195 hom., cov: 32)

Exomes 𝑓: 0.26 ( 51335 hom. )

Consequence

MSH3
NM_002439.5 intron

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.76

Variant links:

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.95).

BP6

Variant 5-80656607-G-C is Benign according to our data. Variant chr5-80656607-G-C is described in ClinVar as [Benign]. Clinvar id is 1251884.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.304 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MSH3	NM_002439.5 linkuse as main transcript	c.358+76G>C		intron_variant		ENST00000265081.7	NP_002430.3	P20585

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Protein	UniProt
MSH3	ENST00000265081.7 linkuse as main transcript	c.358+76G>C	intron_variant	1	NM_002439.5	ENSP00000265081.6	P20585
MSH3	ENST00000658259.1 linkuse as main transcript	c.190+76G>C	intron_variant			ENSP00000499617.1	A0A590UJW0
MSH3	ENST00000667069.1 linkuse as main transcript	c.358+76G>C	intron_variant			ENSP00000499502.1	A0A590UJN8
MSH3	ENST00000670357.1 linkuse as main transcript	n.358+76G>C	intron_variant			ENSP00000499791.1	A0A590UKC9

Frequencies

GnomAD3 genomes

AF:

0.257

AC:

39042

AN:

151954

Hom.:

5191

Cov.:

show subpopulations

Gnomad AFR

AF:

0.279

Gnomad AMI

AF:

0.255

Gnomad AMR

AF:

0.230

Gnomad ASJ

AF:

0.296

Gnomad EAS

AF:

0.0475

Gnomad SAS

AF:

0.317

Gnomad FIN

AF:

0.205

Gnomad MID

AF:

0.326

Gnomad NFE

AF:

0.266

Gnomad OTH

AF:

0.286

GnomAD4 exome

AF:

0.261

AC:

374507

AN:

1434456

Hom.:

51335

AF XY:

0.264

AC XY:

189072

AN XY:

714998

show subpopulations

Gnomad4 AFR exome

AF:

0.280

Gnomad4 AMR exome

AF:

0.163

Gnomad4 ASJ exome

AF:

0.268

Gnomad4 EAS exome

AF:

0.0329

Gnomad4 SAS exome

AF:

0.325

Gnomad4 FIN exome

AF:

0.210

Gnomad4 NFE exome

AF:

0.269

Gnomad4 OTH exome

AF:

0.269

GnomAD4 genome

AF:

0.257

AC:

39056

AN:

152072

Hom.:

5195

Cov.:

AF XY:

0.255

AC XY:

18924

AN XY:

74344

show subpopulations

Gnomad4 AFR

AF:

0.278

Gnomad4 AMR

AF:

0.230

Gnomad4 ASJ

AF:

0.296

Gnomad4 EAS

AF:

0.0476

Gnomad4 SAS

AF:

0.317

Gnomad4 FIN

AF:

0.205

Gnomad4 NFE

AF:

0.266

Gnomad4 OTH

AF:

0.284

Alfa

AF:

0.101

Hom.:

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

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

-0.95

CADD

Benign

0.56

DANN

Benign

0.40

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over