Variant 5-80654689-C-T 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.-39C>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.166 in 1,560,524 control chromosomes in the GnomAD database, including 23,414 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.13 ( 1639 hom., cov: 32)

Exomes 𝑓: 0.17 ( 21775 hom. )

Consequence

MSH3
NM_002439.5 5_prime_UTR

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.00800

Variant links:

Genes affected

DHFR (HGNC:2861): (dihydrofolate reductase) Dihydrofolate reductase converts dihydrofolate into tetrahydrofolate, a methyl group shuttle required for the de novo synthesis of purines, thymidylic acid, and certain amino acids. While the functional dihydrofolate reductase gene has been mapped to chromosome 5, multiple intronless processed pseudogenes or dihydrofolate reductase-like genes have been identified on separate chromosomes. Dihydrofolate reductase deficiency has been linked to megaloblastic anemia. Several transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Mar 2014]

DHFR links:

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=-0.75).

BP6

Variant 5-80654689-C-T is Benign according to our data. Variant chr5-80654689-C-T is described in ClinVar as [Benign]. Clinvar id is 1220684.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.23 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DHFR	NM_000791.4 linkuse as main transcript	c.-200G>A		5_prime_UTR_variant	1/6	ENST00000439211.7
MSH3	NM_002439.5 linkuse as main transcript	c.-39C>T		5_prime_UTR_variant	1/24	ENST00000265081.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MSH3	ENST00000265081.7 linkuse as main transcript	c.-39C>T		5_prime_UTR_variant	1/24	1	NM_002439.5	P2
DHFR	ENST00000439211.7 linkuse as main transcript	c.-200G>A		5_prime_UTR_variant	1/6	1	NM_000791.4	P1	P00374-1

Frequencies

GnomAD3 genomes

AF:

0.134

AC:

20264

AN:

151422

Hom.:

1639

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0478

Gnomad AMI

AF:

0.144

Gnomad AMR

AF:

0.113

Gnomad ASJ

AF:

0.126

Gnomad EAS

AF:

0.0677

Gnomad SAS

AF:

0.241

Gnomad FIN

AF:

0.206

Gnomad MID

AF:

0.115

Gnomad NFE

AF:

0.178

Gnomad OTH

AF:

0.115

GnomAD3 exomes

AF:

0.156

AC:

30664

AN:

196436

Hom.:

2865

AF XY:

0.166

AC XY:

18324

AN XY:

110392

show subpopulations

Gnomad AFR exome

AF:

0.0442

Gnomad AMR exome

AF:

0.0786

Gnomad ASJ exome

AF:

0.121

Gnomad EAS exome

AF:

0.0686

Gnomad SAS exome

AF:

0.239

Gnomad FIN exome

AF:

0.201

Gnomad NFE exome

AF:

0.176

Gnomad OTH exome

AF:

0.150

GnomAD4 exome

AF:

0.169

AC:

238344

AN:

1408996

Hom.:

21775

Cov.:

AF XY:

0.172

AC XY:

120785

AN XY:

701824

show subpopulations

Gnomad4 AFR exome

AF:

0.0413

Gnomad4 AMR exome

AF:

0.0844

Gnomad4 ASJ exome

AF:

0.126

Gnomad4 EAS exome

AF:

0.0672

Gnomad4 SAS exome

AF:

0.240

Gnomad4 FIN exome

AF:

0.201

Gnomad4 NFE exome

AF:

0.174

Gnomad4 OTH exome

AF:

0.154

GnomAD4 genome

AF:

0.134

AC:

20272

AN:

151528

Hom.:

1639

Cov.:

AF XY:

0.136

AC XY:

10053

AN XY:

74026

show subpopulations

Gnomad4 AFR

AF:

0.0478

Gnomad4 AMR

AF:

0.113

Gnomad4 ASJ

AF:

0.126

Gnomad4 EAS

AF:

0.0677

Gnomad4 SAS

AF:

0.242

Gnomad4 FIN

AF:

0.206

Gnomad4 NFE

AF:

0.178

Gnomad4 OTH

AF:

0.112

Alfa

AF:

0.104

Hom.:

291

Bravo

AF:

0.117

Asia WGS

AF:

0.134

AC:

463

AN:

3456

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

-0.75

Cadd

Benign

7.2

Dann

Benign

0.84

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

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