rs604714

Variant names:

• chr11-119099986-C-A
• rs604714
• NM_001382.4:c.643+276G>T

Your query was ambiguous. Multiple possible variants found:

• chr11-119099986-C-A
• chr11-119099986-C-G

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001382.4(DPAGT1):​c.643+276G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.311 in 151,698 control chromosomes in the GnomAD database, including 7,934 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.31 (7934 hom., cov: 30)
• Consequence: DPAGT1 NM_001382.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.236
• Publications: 8 publications found

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 Gene-Disease associations (from GenCC):

• congenital myasthenic syndrome 13

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), PanelApp Australia, Genomics England PanelApp, G2P
• DPAGT1-congenital disorder of glycosylation

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), PanelApp Australia, Orphanet, G2P
• congenital myasthenic syndromes with glycosylation defect

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BP6: Variant 11-119099986-C-A is Benign according to our data. Variant chr11-119099986-C-A is described in ClinVar as Benign. ClinVar VariationId is 680552.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.473 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DPAGT1	NM_001382.4	c.643+276G>T		intron_variant	Intron 4 of 8	ENST00000354202.9	NP_001373.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DPAGT1	ENST00000354202.9	c.643+276G>T		intron_variant	Intron 4 of 8	1	NM_001382.4	ENSP00000346142.4

Frequencies

GnomAD3 genomes AF: 0.312 AC: 47235 AN: 151580 Hom.: 7933 Cov.: 30

Gnomad AFR AF: 0.194

Gnomad AMI AF: 0.383

Gnomad AMR AF: 0.263

Gnomad ASJ AF: 0.447

Gnomad EAS AF: 0.488

Gnomad SAS AF: 0.204

Gnomad FIN AF: 0.378

Gnomad MID AF: 0.307

Gnomad NFE AF: 0.369

Gnomad OTH AF: 0.338

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.311 AC: 47251 AN: 151698 Hom.: 7934 Cov.: 30 AF XY: 0.311 AC XY: 23040 AN XY: 74114

African (AFR) AF: 0.194 AC: 8015 AN: 41334

American (AMR) AF: 0.263 AC: 4003 AN: 15224

Ashkenazi Jewish (ASJ) AF: 0.447 AC: 1551 AN: 3468

East Asian (EAS) AF: 0.489 AC: 2518 AN: 5152

South Asian (SAS) AF: 0.204 AC: 978 AN: 4802

European-Finnish (FIN) AF: 0.378 AC: 3959 AN: 10486

Middle Eastern (MID) AF: 0.316 AC: 93 AN: 294

European-Non Finnish (NFE) AF: 0.369 AC: 25070 AN: 67928

Other (OTH) AF: 0.341 AC: 716 AN: 2102

Alfa AF: 0.319 Hom.: 1327

Bravo AF: 0.303

Asia WGS AF: 0.300 AC: 1049 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Jun 16, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	4.8
DANN	Benign	0.62
PhyloP100		0.24
PromoterAI		-0.038	Neutral
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs604714; hg19: chr11-118970696;