rs643788

chr11-119097048-T-C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

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
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:12
• Conservation: PhyloP100: -0.573

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]

ACMG classification

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	UniProt
DPAGT1	NM_001382.4	c.1177A>G	p.Ile393Val	missense_variant	9/9	ENST00000354202.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DPAGT1	ENST00000354202.9	c.1177A>G	p.Ile393Val	missense_variant	9/9	1	NM_001382.4	P1

Frequencies

GnomAD3 genomes AF: 0.390 AC: 59257 AN: 151838 Hom.: 12148 Cov.: 31

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

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.: 57 AF XY: 0.429 AC XY: 311817 AN XY: 727210

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.: 31 AF XY: 0.392 AC XY: 29121 AN XY: 74266

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:12

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:6

Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
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, no assertion criteria provided	clinical testing	Genome Diagnostics Laboratory, University Medical Center Utrecht	-	- -
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	Genetic Services Laboratory, University of Chicago	Aug 15, 2013	- -

DPAGT1-congenital disorder of glycosylation Benign:2

Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Jul 30, 2021	- -
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. -

DPAGT1-congenital disorder of glycosylation;C3553645:Congenital myasthenic syndrome 13 Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Feb 01, 2024

- -

Acute intermittent porphyria Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

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

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.056
BayesDel_addAF	Benign	-0.61	T
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	N
MetaRNN	Benign	0.0000076	T;T;T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	-0.17	N;N;.
MutationTaster	Benign	1.0	P;P;P
PrimateAI	Benign	0.28	T
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	T
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

Other links and lift over

dbSNP: rs643788; hg19: chr11-118967758; COSMIC: COSV53827927; COSMIC: COSV53827927;