rs8551

chr11-119096814-C-T

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.*184G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.421 in 719,004 control chromosomes in the GnomAD database, including 66,477 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.39 (12042 hom., cov: 32)
  • Exomes 𝑓: 0.43 (54435 hom.)
• Consequence: DPAGT1 NM_001382.4 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: -0.195

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 (BayesDel_noAF=-0.9).
• BP6: Variant 11-119096814-C-T is Benign according to our data. Variant chr11-119096814-C-T is described in ClinVar as [Benign]. Clinvar id is 302745.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.624 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DPAGT1	NM_001382.4	c.*184G>A		3_prime_UTR_variant	9/9	ENST00000354202.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DPAGT1	ENST00000354202.9	c.*184G>A		3_prime_UTR_variant	9/9	1	NM_001382.4	P1

Frequencies

GnomAD3 genomes AF: 0.388 AC: 58869 AN: 151786 Hom.: 12031 Cov.: 32

Gnomad AFR AF: 0.290

Gnomad AMI AF: 0.487

Gnomad AMR AF: 0.329

Gnomad ASJ AF: 0.534

Gnomad EAS AF: 0.641

Gnomad SAS AF: 0.517

Gnomad FIN AF: 0.393

Gnomad MID AF: 0.417

Gnomad NFE AF: 0.422

Gnomad OTH AF: 0.421

GnomAD4 exome AF: 0.430 AC: 243846 AN: 567100 Hom.: 54435 Cov.: 7 AF XY: 0.436 AC XY: 130835 AN XY: 300336

Gnomad4 AFR exome AF: 0.285

Gnomad4 AMR exome AF: 0.271

Gnomad4 ASJ exome AF: 0.550

Gnomad4 EAS exome AF: 0.621

Gnomad4 SAS exome AF: 0.498

Gnomad4 FIN exome AF: 0.384

Gnomad4 NFE exome AF: 0.419

Gnomad4 OTH exome AF: 0.437

GnomAD4 genome AF: 0.388 AC: 58905 AN: 151904 Hom.: 12042 Cov.: 32 AF XY: 0.390 AC XY: 28980 AN XY: 74240

Gnomad4 AFR AF: 0.290

Gnomad4 AMR AF: 0.328

Gnomad4 ASJ AF: 0.534

Gnomad4 EAS AF: 0.642

Gnomad4 SAS AF: 0.516

Gnomad4 FIN AF: 0.393

Gnomad4 NFE AF: 0.422

Gnomad4 OTH AF: 0.425

Alfa AF: 0.393 Hom.: 4979

Bravo AF: 0.378

Asia WGS AF: 0.542 AC: 1889 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

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

- -

DPAGT1-congenital disorder of glycosylation Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 12, 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. -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 29, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
Cadd	Benign	0.26
Dann	Benign	0.36
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs8551; hg19: chr11-118967524; COSMIC: COSV53830464; COSMIC: COSV53830464;