rs7759

Variant names:

• chr11-119096581-A-G
• rs7759
• NM_001382.4:c.*417T>C

Your query was ambiguous. Multiple possible variants found:

• chr11-119096581-A-G
• chr11-119096581-A-C
• chr11-119096581-A-T

Variant summary

Our verdict is Benign. The variant received -17 ACMG points: 0P and 17B. BP4 BP6_Very_Strong BA1

The NM_001382.4(DPAGT1):​c.*417T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.315 in 306,606 control chromosomes in the GnomAD database, including 16,986 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.30 (7701 hom., cov: 32)
  • Exomes 𝑓: 0.33 (9285 hom.)
• Consequence: DPAGT1 NM_001382.4 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: 2.51
• Publications: 21 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), Genomics England PanelApp, G2P
• DPAGT1-congenital disorder of glycosylation

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

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -17 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.16).
• BP6: Variant 11-119096581-A-G is Benign according to our data. Variant chr11-119096581-A-G is described in ClinVar as Benign. ClinVar VariationId is 302741.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.482 is higher than 0.05.

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.*417T>C		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.*417T>C		3_prime_UTR	Exon 9 of 9	ENSP00000346142.4	Q9H3H5-1
	DPAGT1	ENST00000409993.6	TSL:2	c.*417T>C		3_prime_UTR	Exon 11 of 11	ENSP00000386597.2	Q9H3H5-1
	DPAGT1	ENST00000867497.1		c.*417T>C		3_prime_UTR	Exon 10 of 10	ENSP00000537556.1

Frequencies

GnomAD3 genomes AF: 0.301 AC: 45680 AN: 151944 Hom.: 7695 Cov.: 32

Gnomad AFR AF: 0.152

Gnomad AMI AF: 0.384

Gnomad AMR AF: 0.262

Gnomad ASJ AF: 0.450

Gnomad EAS AF: 0.497

Gnomad SAS AF: 0.204

Gnomad FIN AF: 0.375

Gnomad MID AF: 0.316

Gnomad NFE AF: 0.370

Gnomad OTH AF: 0.331

GnomAD4 exome AF: 0.330 AC: 50969 AN: 154544 Hom.: 9285 Cov.: 0 AF XY: 0.319 AC XY: 26482 AN XY: 82888

African (AFR) AF: 0.135 AC: 675 AN: 5012

American (AMR) AF: 0.248 AC: 1339 AN: 5404

Ashkenazi Jewish (ASJ) AF: 0.447 AC: 1781 AN: 3988

East Asian (EAS) AF: 0.486 AC: 3562 AN: 7336

South Asian (SAS) AF: 0.198 AC: 4847 AN: 24524

European-Finnish (FIN) AF: 0.353 AC: 2679 AN: 7590

Middle Eastern (MID) AF: 0.382 AC: 231 AN: 604

European-Non Finnish (NFE) AF: 0.359 AC: 33040 AN: 91958

Other (OTH) AF: 0.346 AC: 2815 AN: 8128

GnomAD4 genome AF: 0.301 AC: 45707 AN: 152062 Hom.: 7701 Cov.: 32 AF XY: 0.300 AC XY: 22282 AN XY: 74324

African (AFR) AF: 0.152 AC: 6316 AN: 41480

American (AMR) AF: 0.262 AC: 4001 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.450 AC: 1560 AN: 3470

East Asian (EAS) AF: 0.498 AC: 2577 AN: 5174

South Asian (SAS) AF: 0.203 AC: 979 AN: 4822

European-Finnish (FIN) AF: 0.375 AC: 3955 AN: 10540

Middle Eastern (MID) AF: 0.327 AC: 96 AN: 294

European-Non Finnish (NFE) AF: 0.370 AC: 25170 AN: 67972

Other (OTH) AF: 0.333 AC: 704 AN: 2112

Alfa AF: 0.347 Hom.: 12096

Bravo AF: 0.290

Asia WGS AF: 0.305 AC: 1063 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	Acute intermittent porphyria (1)
-	-	1	Congenital disorder of glycosylation (1)
-	-	1	DPAGT1-congenital disorder of glycosylation (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.16
CADD	Benign	14
DANN	Benign	0.86
PhyloP100		2.5
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
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: rs7759; hg19: chr11-118967291; COSMIC: COSV53830457; COSMIC: COSV53830457;