rs551963408

Positions:

chr11-119097048-T-C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001382.4(DPAGT1):c.1177A>G(p.Ile393Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.423 in 1,613,754 control chromosomes in the GnomAD database, including 147,791 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.39 ( 12160 hom., cov: 31)

Exomes 𝑓: 0.43 ( 135631 hom. )

Consequence

DPAGT1
NM_001382.4 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:13

Conservation

PhyloP100: -0.573

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=7.635585E-6).

BP6

Variant 11-119097048-T-C is Benign according to our data. Variant chr11-119097048-T-C is described in ClinVar as [Benign]. Clinvar id is 93728.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-119097048-T-C is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.625 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DPAGT1	NM_001382.4 linkuse as main transcript	c.1177A>G	p.Ile393Val	missense_variant	9/9	ENST00000354202.9	NP_001373.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DPAGT1	ENST00000354202.9 linkuse as main transcript	c.1177A>G	p.Ile393Val	missense_variant	9/9	1	NM_001382.4	ENSP00000346142	P1	Q9H3H5-1

Frequencies

GnomAD3 genomes

AF:

0.390

AC:

59257

AN:

151838

Hom.:

12148

Cov.:

show subpopulations

Gnomad AFR

AF:

0.297

Gnomad AMI

AF:

0.487

Gnomad AMR

AF:

0.329

Gnomad ASJ

AF:

0.557

Gnomad EAS

AF:

0.642

Gnomad SAS

AF:

0.496

Gnomad FIN

AF:

0.393

Gnomad MID

AF:

0.430

Gnomad NFE

AF:

0.423

Gnomad OTH

AF:

0.425

GnomAD3 exomes

AF:

0.418

AC:

105048

AN:

251260

Hom.:

23409

AF XY:

0.428

AC XY:

58095

AN XY:

135826

show subpopulations

Gnomad AFR exome

AF:

0.295

Gnomad AMR exome

AF:

0.256

Gnomad ASJ exome

AF:

0.573

Gnomad EAS exome

AF:

0.639

Gnomad SAS exome

AF:

0.482

Gnomad FIN exome

AF:

0.385

Gnomad NFE exome

AF:

0.424

Gnomad OTH exome

AF:

0.434

GnomAD4 exome

AF:

0.426

AC:

622857

AN:

1461798

Hom.:

135631

Cov.:

AF XY:

0.429

AC XY:

311817

AN XY:

727210

show subpopulations

Gnomad4 AFR exome

AF:

0.291

Gnomad4 AMR exome

AF:

0.263

Gnomad4 ASJ exome

AF:

0.574

Gnomad4 EAS exome

AF:

0.625

Gnomad4 SAS exome

AF:

0.482

Gnomad4 FIN exome

AF:

0.387

Gnomad4 NFE exome

AF:

0.423

Gnomad4 OTH exome

AF:

0.440

GnomAD4 genome

AF:

0.390

AC:

59299

AN:

151956

Hom.:

12160

Cov.:

AF XY:

0.392

AC XY:

29121

AN XY:

74266

show subpopulations

Gnomad4 AFR

AF:

0.297

Gnomad4 AMR

AF:

0.329

Gnomad4 ASJ

AF:

0.557

Gnomad4 EAS

AF:

0.643

Gnomad4 SAS

AF:

0.495

Gnomad4 FIN

AF:

0.393

Gnomad4 NFE

AF:

0.423

Gnomad4 OTH

AF:

0.429

Alfa

AF:

0.433

Hom.:

37772

Bravo

AF:

0.381

TwinsUK

AF:

0.421

AC:

1560

ALSPAC

AF:

0.431

AC:

1662

ESP6500AA

AF:

0.297

AC:

1307

ESP6500EA

AF:

0.433

AC:

3723

ExAC

AF:

0.421

AC:

51147

Asia WGS

AF:

0.534

AC:

1859

AN:

3478

EpiCase

AF:

0.445

EpiControl

AF:

0.438

ClinVar

Significance: Benign

Submissions summary: Benign:13

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:6

Benign, no assertion criteria provided	clinical testing	Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	-	- -
Benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Jul 10, 2012	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Dec 02, 2015	This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Benign, no assertion criteria provided	clinical testing	Genome Diagnostics Laboratory, University Medical Center Utrecht	-	- -
Benign, criteria provided, single submitter	clinical testing	Genetic Services Laboratory, University of Chicago	Aug 15, 2013	- -

DPAGT1-congenital disorder of glycosylation

Benign:2

Benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jan 13, 2018	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -
Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Jul 30, 2021	- -

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

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Feb 01, 2024

- -

Congenital disorder of glycosylation

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Congenital myasthenic syndrome 13

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 30, 2021

- -

Acute intermittent porphyria

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

not provided

Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.056

BayesDel_addAF

Benign

-0.61

BayesDel_noAF

Benign

-0.50

CADD

Benign

0.29

DANN

Benign

0.38

DEOGEN2

Benign

0.18

T;T;.

Eigen

Benign

-2.0

Eigen_PC

Benign

-2.0

FATHMM_MKL

Benign

0.026

LIST_S2

Benign

0.61

.;T;T

MetaRNN

Benign

0.0000076

T;T;T

MetaSVM

Benign

-0.98

MutationAssessor

Benign

-0.17

N;N;.

MutationTaster

Benign

1.0

P;P;P

PrimateAI

Benign

0.28

PROVEAN

Benign

-0.36

N;N;.

REVEL

Benign

0.20

Sift

Benign

0.55

T;T;.

Sift4G

Benign

0.53

T;T;.

Polyphen

0.0

B;B;.

Vest4

0.0040

MPC

0.42

ClinPred

0.0019

GERP RS

-4.2

RBP_binding_hub_radar

0.92

RBP_regulation_power_radar

2.0

Varity_R

0.027

gMVP

0.23

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