Variant 19-45786079-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_004943.2(DMWD):c.1417G>A(p.Ala473Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000954 in 1,363,198 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 34)

Exomes 𝑓: 0.0000095 ( 0 hom. )

Consequence

DMWD
NM_004943.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.242

Variant links:

Genes affected

DMWD (HGNC:2936): (DM1 locus, WD repeat containing) Predicted to be located in dendrite; nucleus; and perikaryon. [provided by Alliance of Genome Resources, Apr 2022]

DMWD links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.084296346).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DMWD	NM_004943.2 linkuse as main transcript	c.1417G>A	p.Ala473Thr	missense_variant	3/5	ENST00000270223.7	NP_004934.1	Q09019Q8WUW6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DMWD	ENST00000270223.7 linkuse as main transcript	c.1417G>A	p.Ala473Thr	missense_variant	3/5	1	NM_004943.2	ENSP00000270223.5		Q09019
DMWD	ENST00000377735.7 linkuse as main transcript	c.1417G>A	p.Ala473Thr	missense_variant	3/4	5		ENSP00000366964.3		G5E9A7

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000332

AC:

AN:

120536

Hom.:

AF XY:

0.0000307

AC XY:

AN XY:

65092

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:

0.0000854

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000954

AC:

AN:

1363198

Hom.:

Cov.:

AF XY:

0.00000599

AC XY:

AN XY:

668262

show subpopulations

Gnomad4 AFR exome

AF:

0.0000646

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000137

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000753

Gnomad4 OTH exome

AF:

0.0000178

GnomAD4 genome

Cov.:

ExAC

AF:

0.0000356

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

May 23, 2023

The c.1417G>A (p.A473T) alteration is located in exon 3 (coding exon 3) of the DMWD gene. This alteration results from a G to A substitution at nucleotide position 1417, causing the alanine (A) at amino acid position 473 to be replaced by a threonine (T). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.065

BayesDel_addAF

Benign

-0.19

BayesDel_noAF

Benign

-0.52

CADD

Benign

0.35

DANN

Benign

0.96

DEOGEN2

Benign

0.0095

T;T

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.29

LIST_S2

Benign

0.55

T;T

M_CAP

Uncertain

0.16

MetaRNN

Benign

0.084

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.55

.;N

PrimateAI

Uncertain

0.71

PROVEAN

Benign

-0.49

N;N

REVEL

Benign

0.084

Sift

Benign

0.27

T;T

Sift4G

Benign

0.44

T;T

Polyphen

0.0

B;B

Vest4

0.11

MutPred

0.26

Gain of glycosylation at A473 (P = 7e-04);Gain of glycosylation at A473 (P = 7e-04);

MVP

0.68

MPC

0.75

ClinPred

0.027

GERP RS

-4.3

Varity_R

0.031

gMVP

0.12

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