rs74992671

Variant names:

• chr11-119096839-C-T
• rs74992671
• NM_001382.4:c.*159G>A

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP6 BS1 BS2

The NM_001382.4(DPAGT1):​c.*159G>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 0.000772 in 880,762 control chromosomes in the GnomAD database, including 5 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

• Frequency:
  • Genomes: 𝑓 0.0030 (4 hom., cov: 32)
  • Exomes 𝑓: 0.00031 (1 hom.)
• Consequence: DPAGT1 NM_001382.4 3_prime_UTR
• Clinical Significance: Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1 B:1
• Conservation: PhyloP100: 0.0390
• Publications: 0 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: PanelApp Australia, G2P, Genomics England PanelApp, Labcorp Genetics (formerly Invitae)
• DPAGT1-congenital disorder of glycosylation

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

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BP6: Variant 11-119096839-C-T is Benign according to our data. Variant chr11-119096839-C-T is described in ClinVar as Conflicting_classifications_of_pathogenicity. ClinVar VariationId is 368940.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00297 (452/152180) while in subpopulation AFR AF = 0.0105 (434/41500). AF 95% confidence interval is 0.00965. There are 4 homozygotes in GnomAd4. There are 201 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 4 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001382.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DPAGT1	NM_001382.4	MANE Select	c.*159G>A		3_prime_UTR	Exon 9 of 9	NP_001373.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DPAGT1	ENST00000354202.9	TSL:1 MANE Select	c.*159G>A		3_prime_UTR	Exon 9 of 9	ENSP00000346142.4	Q9H3H5-1
	DPAGT1	ENST00000409993.6	TSL:2	c.*159G>A		3_prime_UTR	Exon 11 of 11	ENSP00000386597.2	Q9H3H5-1
	DPAGT1	ENST00000867497.1		c.*159G>A		3_prime_UTR	Exon 10 of 10	ENSP00000537556.1

Frequencies

GnomAD3 genomes AF: 0.00297 AC: 451 AN: 152062 Hom.: 4 Cov.: 32

Gnomad AFR AF: 0.0105

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000590

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000882

Gnomad OTH AF: 0.00143

GnomAD4 exome AF: 0.000313 AC: 228 AN: 728582 Hom.: 1 Cov.: 9 AF XY: 0.000248 AC XY: 94 AN XY: 379266

African (AFR) AF: 0.0106 AC: 193 AN: 18178

American (AMR) AF: 0.000221 AC: 7 AN: 31644

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19622

East Asian (EAS) AF: 0.00 AC: 0 AN: 32536

South Asian (SAS) AF: 0.00 AC: 0 AN: 62336

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 42854

Middle Eastern (MID) AF: 0.000357 AC: 1 AN: 2802

European-Non Finnish (NFE) AF: 0.0000145 AC: 7 AN: 482778

Other (OTH) AF: 0.000558 AC: 20 AN: 35832

GnomAD4 genome AF: 0.00297 AC: 452 AN: 152180 Hom.: 4 Cov.: 32 AF XY: 0.00270 AC XY: 201 AN XY: 74402

African (AFR) AF: 0.0105 AC: 434 AN: 41500

American (AMR) AF: 0.000589 AC: 9 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3466

East Asian (EAS) AF: 0.00 AC: 0 AN: 5190

South Asian (SAS) AF: 0.00 AC: 0 AN: 4822

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10594

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000882 AC: 6 AN: 68010

Other (OTH) AF: 0.00142 AC: 3 AN: 2114

Alfa AF: 0.00162 Hom.: 0

Bravo AF: 0.00337

Asia WGS AF: 0.000577 AC: 2 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Conflicting classifications of pathogenicity

Revision: criteria provided, conflicting classifications

Pathogenic	VUS	Benign	Condition
-	-	1	Acute intermittent porphyria (1)
-	1	-	DPAGT1-congenital disorder of glycosylation (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	2.2
DANN	Benign	0.59
PhyloP100		0.039
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=100/0	polymorphism

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: rs74992671; hg19: chr11-118967549;