rs387907243

Positions:

• chr11-119100777-C-A
• chr11-119100777-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP3

The NM_001382.4(DPAGT1):​c.349G>T​(p.Val117Leu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000657 in 152,314 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.0000066 (0 hom., cov: 32)
• Consequence: DPAGT1 NM_001382.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.91

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 Uncertain_significance. Variant got 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.766

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DPAGT1	NM_001382.4	c.349G>T	p.Val117Leu	missense_variant	3/9	ENST00000354202.9	NP_001373.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DPAGT1	ENST00000354202.9	c.349G>T	p.Val117Leu	missense_variant	3/9	1	NM_001382.4	ENSP00000346142	P1

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152196 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome Cov.: 33

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152314 Hom.: 0 Cov.: 32 AF XY: 0.0000134 AC XY: 1 AN XY: 74482

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000207

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.00

ExAC AF: 0.00000824 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.91
BayesDel_addAF	Pathogenic	0.20	D
BayesDel_noAF	Pathogenic	0.15
CADD	Pathogenic	26
DANN	Benign	0.93
DEOGEN2	Uncertain	0.72	D;D
Eigen	Uncertain	0.29
Eigen_PC	Uncertain	0.41
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Pathogenic	0.99	.;D
M_CAP	Pathogenic	0.34	D
MetaRNN	Pathogenic	0.77	D;D
MetaSVM	Uncertain	0.29	D
MutationAssessor	Benign	1.5	L;L
MutationTaster	Benign	1.0	D;D;D
PrimateAI	Pathogenic	0.93	D
PROVEAN	Uncertain	-2.4	N;N
REVEL	Pathogenic	0.76
Sift	Benign	0.67	T;T
Sift4G	Benign	0.58	T;T
Polyphen		0.16	B;B
Vest4		0.82
MutPred		0.73		Gain of helix (P = 0.132);Gain of helix (P = 0.132);
MVP		0.96
MPC		1.3
ClinPred		0.97	D
GERP RS		5.5
Varity_R		0.80
gMVP		0.79

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs387907243; hg19: chr11-118971487;