Variant rs780659624 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_004409.5(DMPK):c.1324G>T(p.Val442Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000144 in 1,389,940 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

DMPK
NM_004409.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.100

Variant links:

Genes affected

DMPK (HGNC:2933): (DM1 protein kinase) The protein encoded by this gene is a serine-threonine kinase that is closely related to other kinases that interact with members of the Rho family of small GTPases. Substrates for this enzyme include myogenin, the beta-subunit of the L-type calcium channels, and phospholemman. The 3' untranslated region of this gene contains 5-38 copies of a CTG trinucleotide repeat. Expansion of this unstable motif to 50-5,000 copies causes myotonic dystrophy type I, which increases in severity with increasing repeat element copy number. Repeat expansion is associated with condensation of local chromatin structure that disrupts the expression of genes in this region. Several alternatively spliced transcript variants of this gene have been described, but the full-length nature of some of these variants has not been determined. [provided by RefSeq, Jul 2016]

DMPK links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.057032228).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DMPK	NM_004409.5 linkuse as main transcript	c.1324G>T	p.Val442Leu	missense_variant	10/15	ENST00000291270.9	NP_004400.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DMPK	ENST00000291270.9 linkuse as main transcript	c.1324G>T	p.Val442Leu	missense_variant	10/15	5	NM_004409.5	ENSP00000291270	A2	Q09013-9

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000539

AC:

AN:

185618

Hom.:

AF XY:

0.00

AC XY:

AN XY:

102592

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000110

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000144

AC:

AN:

1389940

Hom.:

Cov.:

AF XY:

0.00000145

AC XY:

AN XY:

690048

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000184

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ExAC

AF:

0.00000824

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.087

BayesDel_addAF

Benign

-0.18

BayesDel_noAF

Benign

-0.50

CADD

Benign

7.7

DANN

Benign

0.83

DEOGEN2

Benign

0.14

T;.;.;.;.;.;.;T

Eigen

Benign

-1.0

Eigen_PC

Benign

-1.0

FATHMM_MKL

Benign

0.13

LIST_S2

Benign

0.74

T;T;T;T;.;T;T;T

M_CAP

Benign

0.018

MetaRNN

Benign

0.057

T;T;T;T;T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.9

L;.;.;.;.;.;.;.

MutationTaster

Benign

1.0

N;N;N;N;N;N

PrimateAI

Benign

0.45

PROVEAN

Benign

-0.49

N;.;N;N;N;.;N;.

REVEL

Benign

0.045

Sift

Benign

0.62

T;.;T;T;T;.;T;.

Sift4G

Benign

0.51

T;T;T;T;T;T;T;D

Polyphen

0.0030

B;.;.;.;.;.;B;.

Vest4

0.057

MutPred

0.092

Gain of relative solvent accessibility (P = 0.0479);.;.;.;.;.;.;.;

MVP

0.53

MPC

0.34

ClinPred

0.022

GERP RS

2.3

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.037

gMVP

0.22

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over