rs199994118

Variant names:

• chr11-119100796-G-A
• rs199994118
• NM_001382.4:c.330C>T

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_Strong BP6 BP7

The NM_001382.4(DPAGT1):​c.330C>T​(p.Phe110Phe) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000594 in 1,614,114 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 0.00054 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00060 (0 hom.)
• Consequence: DPAGT1 NM_001382.4 synonymous
• Clinical Significance: Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1 B:3
• Conservation: PhyloP100: 1.87
• 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: 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: Likely_benign. The variant received -6 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.5).
• BP6: Variant 11-119100796-G-A is Benign according to our data. Variant chr11-119100796-G-A is described in ClinVar as Conflicting_classifications_of_pathogenicity. ClinVar VariationId is 540462.
• BP7: Synonymous conserved (PhyloP=1.87 with no splicing effect.

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DPAGT1	NM_001382.4	MANE Select	c.330C>T	p.Phe110Phe	synonymous	Exon 3 of 9	NP_001373.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DPAGT1	ENST00000354202.9	TSL:1 MANE Select	c.330C>T	p.Phe110Phe	synonymous	Exon 3 of 9	ENSP00000346142.4
	DPAGT1	ENST00000409993.6	TSL:2	c.330C>T	p.Phe110Phe	synonymous	Exon 5 of 11	ENSP00000386597.2
	DPAGT1	ENST00000682791.1		c.243C>T	p.Phe81Phe	synonymous	Exon 2 of 8	ENSP00000507312.1

Frequencies

GnomAD3 genomes AF: 0.000539 AC: 82 AN: 152222 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.0307

Gnomad AMR AF: 0.000327

Gnomad ASJ AF: 0.00173

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000603

Gnomad OTH AF: 0.000956

GnomAD2 exomes AF: 0.000394 AC: 99 AN: 251450 AF XY: 0.000471

Gnomad AFR exome AF: 0.0000615

Gnomad AMR exome AF: 0.000202

Gnomad ASJ exome AF: 0.00298

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000501

Gnomad OTH exome AF: 0.000652

GnomAD4 exome AF: 0.000600 AC: 877 AN: 1461892 Hom.: 0 Cov.: 33 AF XY: 0.000619 AC XY: 450 AN XY: 727248

African (AFR) AF: 0.0000896 AC: 3 AN: 33480

American (AMR) AF: 0.000134 AC: 6 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00256 AC: 67 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86258

European-Finnish (FIN) AF: 0.0000187 AC: 1 AN: 53420

Middle Eastern (MID) AF: 0.000347 AC: 2 AN: 5766

European-Non Finnish (NFE) AF: 0.000677 AC: 753 AN: 1112012

Other (OTH) AF: 0.000745 AC: 45 AN: 60396

GnomAD4 genome AF: 0.000539 AC: 82 AN: 152222 Hom.: 0 Cov.: 32 AF XY: 0.000619 AC XY: 46 AN XY: 74368

African (AFR) AF: 0.00 AC: 0 AN: 41450

American (AMR) AF: 0.000327 AC: 5 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.00173 AC: 6 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5196

South Asian (SAS) AF: 0.00 AC: 0 AN: 4832

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10626

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.000603 AC: 41 AN: 68034

Other (OTH) AF: 0.000956 AC: 2 AN: 2092

Alfa AF: 0.000654 Hom.: 0

Bravo AF: 0.000737

EpiCase AF: 0.000545

EpiControl AF: 0.000474

ClinVar

ClinVar submissions as Germline

Significance: Conflicting classifications of pathogenicity

Revision: criteria provided, conflicting classifications

Pathogenic	VUS	Benign	Condition
-	1	-	DPAGT1-congenital disorder of glycosylation (1)
-	-	1	DPAGT1-congenital disorder of glycosylation;C3553645:Congenital myasthenic syndrome 13 (1)
-	-	1	DPAGT1-related disorder (1)
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_noAF	Benign	-0.50
CADD	Benign	13
DANN	Benign	0.89
PhyloP100		1.9
PromoterAI		-0.0068	Neutral
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.15		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: rs199994118; hg19: chr11-118971506;