Variant 11-119097296-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001382.4(DPAGT1):c.1007T>C(p.Val336Ala) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,880 control chromosomes in the GnomAD database, with no homozygous occurrence. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

DPAGT1
NM_001382.4 missense, splice_region

Scores

Splicing: ADA: 0.02719

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.53

Variant links:

Genes affected

DPAGT1 (HGNC:2995): (dolichyl-phosphate N-acetylglucosaminephosphotransferase 1) The protein encoded by this gene is an enzyme that catalyzes the first step in the dolichol-linked oligosaccharide pathway for glycoprotein biosynthesis. This enzyme belongs to the glycosyltransferase family 4. This protein is an integral membrane protein of the endoplasmic reticulum. The congenital disorder of glycosylation type Ij is caused by mutation in the gene encoding this enzyme. [provided by RefSeq, Jul 2008]

DPAGT1 links:

DPAGT1 (HGNC:):

DPAGT1 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DPAGT1	NM_001382.4 linkuse as main transcript	c.1007T>C	p.Val336Ala	missense_variant, splice_region_variant	8/9	ENST00000354202.9	NP_001373.2	Q9H3H5-1A0A024R3H8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DPAGT1	ENST00000354202.9 linkuse as main transcript	c.1007T>C	p.Val336Ala	missense_variant, splice_region_variant	8/9	1	NM_001382.4	ENSP00000346142.4		Q9H3H5-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461880

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

727242

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:

0.00

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

DPAGT1-congenital disorder of glycosylation;C3553645:Congenital myasthenic syndrome 13

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 13, 2018

This variant is not present in population databases (ExAC no frequency) and has not been reported in the literature in individuals with a DPAGT1-related disease. This sequence change replaces valine with alanine at codon 336 of the DPAGT1 protein (p.Val336Ala). The valine residue is highly conserved and there is a small physicochemical difference between valine and alanine. Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C25"). In summary, this variant is a novel missense change with uncertain impact on protein function. It has been classified as a Variant of Uncertain Significance. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.069

BayesDel_addAF

Pathogenic

0.20

BayesDel_noAF

Uncertain

0.050

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Uncertain

0.61

D;D;.

Eigen

Benign

0.059

Eigen_PC

Benign

0.16

FATHMM_MKL

Uncertain

0.93

LIST_S2

Benign

0.62

.;T;T

M_CAP

Pathogenic

0.32

MetaRNN

Uncertain

0.54

D;D;D

MetaSVM

Uncertain

0.47

MutationAssessor

Uncertain

2.1

M;M;.

PrimateAI

Uncertain

0.52

PROVEAN

Uncertain

-3.1

D;D;.

REVEL

Pathogenic

0.65

Sift

Benign

0.11

T;T;.

Sift4G

Benign

0.076

T;T;.

Polyphen

0.034

B;B;.

Vest4

0.21

MutPred

0.46

Loss of ubiquitination at K335 (P = 0.0638);Loss of ubiquitination at K335 (P = 0.0638);.;

MVP

0.96

MPC

0.62

ClinPred

0.76

GERP RS

4.1

RBP_binding_hub_radar

0.97

RBP_regulation_power_radar

2.7

Varity_R

0.38

gMVP

0.74

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.027

dbscSNV1_RF

Benign

0.24

SpliceAI score (max)

0.010

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