rs145206990

Positions:

• chr11-119097569-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_001382.4(DPAGT1):​c.918-18G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0138 in 1,613,696 control chromosomes in the GnomAD database, including 207 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0083 (4 hom., cov: 32)
  • Exomes 𝑓: 0.014 (203 hom.)
• Consequence: DPAGT1 NM_001382.4 intron
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:6
• Conservation: PhyloP100: 0.0830

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=-0.76).
• BP6: Variant 11-119097569-C-T is Benign according to our data. Variant chr11-119097569-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 258077.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00834 (1270/152272) while in subpopulation NFE AF= 0.0153 (1042/68024). AF 95% confidence interval is 0.0145. There are 4 homozygotes in gnomad4. There are 533 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 4 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DPAGT1	NM_001382.4	c.918-18G>A		intron_variant		ENST00000354202.9	NP_001373.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DPAGT1	ENST00000354202.9	c.918-18G>A		intron_variant		1	NM_001382.4	ENSP00000346142	P1

Frequencies

GnomAD3 genomes AF: 0.00835 AC: 1270 AN: 152154 Hom.: 4 Cov.: 32

Gnomad AFR AF: 0.00328

Gnomad AMI AF: 0.00219

Gnomad AMR AF: 0.00341

Gnomad ASJ AF: 0.000288

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00373

Gnomad FIN AF: 0.000660

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0153

Gnomad OTH AF: 0.00575

GnomAD3 exomes AF: 0.00787 AC: 1979 AN: 251452 Hom.: 21 AF XY: 0.00799 AC XY: 1086 AN XY: 135910

Gnomad AFR exome AF: 0.00234

Gnomad AMR exome AF: 0.00332

Gnomad ASJ exome AF: 0.000595

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00346

Gnomad FIN exome AF: 0.00171

Gnomad NFE exome AF: 0.0143

Gnomad OTH exome AF: 0.00831

GnomAD4 exome AF: 0.0144 AC: 20987 AN: 1461424 Hom.: 203 Cov.: 33 AF XY: 0.0139 AC XY: 10124 AN XY: 727046

Gnomad4 AFR exome AF: 0.00218

Gnomad4 AMR exome AF: 0.00351

Gnomad4 ASJ exome AF: 0.000689

Gnomad4 EAS exome AF: 0.0000252

Gnomad4 SAS exome AF: 0.00395

Gnomad4 FIN exome AF: 0.00208

Gnomad4 NFE exome AF: 0.0176

Gnomad4 OTH exome AF: 0.0124

GnomAD4 genome AF: 0.00834 AC: 1270 AN: 152272 Hom.: 4 Cov.: 32 AF XY: 0.00716 AC XY: 533 AN XY: 74454

Gnomad4 AFR AF: 0.00327

Gnomad4 AMR AF: 0.00340

Gnomad4 ASJ AF: 0.000288

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00373

Gnomad4 FIN AF: 0.000660

Gnomad4 NFE AF: 0.0153

Gnomad4 OTH AF: 0.00569

Alfa AF: 0.00998 Hom.: 3

Bravo AF: 0.00850

Asia WGS AF: 0.00346 AC: 12 AN: 3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:2

Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Sep 19, 2016	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. -

DPAGT1-congenital disorder of glycosylation;C3553645:Congenital myasthenic syndrome 13 Benign:2

Likely benign, criteria provided, single submitter	clinical testing	Fulgent Genetics, Fulgent Genetics	Nov 23, 2021	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 31, 2024	- -

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Apr 01, 2023	DPAGT1: BS1, BS2 -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.76
CADD	Benign	13
DANN	Benign	0.57

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: rs145206990; hg19: chr11-118968279;