NM_001382.4:c.1217A>T

Variant names:

• chr11-119097008-T-A
• rs753954658
• NM_001382.4:c.1217A>T

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2 PP3

The NM_001382.4(DPAGT1):​c.1217A>T​(p.Tyr406Phe) variant causes a missense change. The variant allele was found at a frequency of 0.00000658 in 152,084 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. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. Y406C) has been classified as Uncertain significance.

• Frequency: Genomes: 𝑓 0.0000066 (0 hom., cov: 32)
• Consequence: DPAGT1 NM_001382.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.74
• Publications: 1 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: Uncertain_significance. The variant received 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.76

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.1217A>T	p.Tyr406Phe	missense	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.1217A>T	p.Tyr406Phe	missense	Exon 9 of 9	ENSP00000346142.4	Q9H3H5-1
	DPAGT1	ENST00000409993.6	TSL:2	c.1217A>T	p.Tyr406Phe	missense	Exon 11 of 11	ENSP00000386597.2	Q9H3H5-1
	DPAGT1	ENST00000867497.1		c.1217A>T	p.Tyr406Phe	missense	Exon 10 of 10	ENSP00000537556.1

Frequencies

GnomAD3 genomes AF: 0.00000658 AC: 1 AN: 152084 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.: 30

GnomAD4 genome AF: 0.00000658 AC: 1 AN: 152084 Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1 AN XY: 74280

African (AFR) AF: 0.00 AC: 0 AN: 41398

American (AMR) AF: 0.00 AC: 0 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5192

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10584

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

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68018

Other (OTH) AF: 0.00 AC: 0 AN: 2094

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.22
BayesDel_addAF	Uncertain	0.15	D
BayesDel_noAF	Uncertain	-0.030
CADD	Benign	20
DANN	Benign	0.92
DEOGEN2	Benign	0.41	T
Eigen	Benign	0.12
Eigen_PC	Uncertain	0.22
FATHMM_MKL	Pathogenic	1.0	D
LIST_S2	Uncertain	0.92	D
M_CAP	Uncertain	0.19	D
MetaRNN	Pathogenic	0.76	D
MetaSVM	Uncertain	0.18	D
MutationAssessor	Benign	1.6	L
PhyloP100		5.7
PrimateAI	Uncertain	0.73	T
PROVEAN	Uncertain	-3.0	D
REVEL	Pathogenic	0.65
Sift	Benign	0.61	T
Sift4G	Benign	0.44	T
Polyphen		0.74	P
Vest4		0.56
MutPred		0.63		Gain of MoRF binding (P = 0.0744)
MVP		0.93
MPC		1.4
ClinPred		0.92	D
GERP RS		4.8
Varity_R		0.33
gMVP		0.55
Mutation Taster		=32/68	disease causing

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: rs753954658; hg19: chr11-118967718;