chr11-119097048-T-C

Variant names:

• chr11-119097048-T-C
• rs643788
• NM_001382.4:c.1177A>G

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001382.4(DPAGT1):​c.1177A>G​(p.Ile393Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.423 in 1,613,754 control chromosomes in the GnomAD database, including 147,791 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.39 (12160 hom., cov: 31)
  • Exomes 𝑓: 0.43 (135631 hom.)
• Consequence: DPAGT1 NM_001382.4 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:13
• Conservation: PhyloP100: -0.573
• Publications: 66 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: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=7.635585E-6).
• BP6: Variant 11-119097048-T-C is Benign according to our data. Variant chr11-119097048-T-C is described in ClinVar as Benign. ClinVar VariationId is 93728.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.625 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.1177A>G	p.Ile393Val	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.1177A>G	p.Ile393Val	missense	Exon 9 of 9	ENSP00000346142.4
	DPAGT1	ENST00000409993.6	TSL:2	c.1177A>G	p.Ile393Val	missense	Exon 11 of 11	ENSP00000386597.2
	DPAGT1	ENST00000867497.1		c.1177A>G	p.Ile393Val	missense	Exon 10 of 10	ENSP00000537556.1

Frequencies

GnomAD3 genomes AF: 0.390 AC: 59257 AN: 151838 Hom.: 12148 Cov.: 31

Gnomad AFR AF: 0.297

Gnomad AMI AF: 0.487

Gnomad AMR AF: 0.329

Gnomad ASJ AF: 0.557

Gnomad EAS AF: 0.642

Gnomad SAS AF: 0.496

Gnomad FIN AF: 0.393

Gnomad MID AF: 0.430

Gnomad NFE AF: 0.423

Gnomad OTH AF: 0.425

GnomAD2 exomes AF: 0.418 AC: 105048 AN: 251260 AF XY: 0.428

Gnomad AFR exome AF: 0.295

Gnomad AMR exome AF: 0.256

Gnomad ASJ exome AF: 0.573

Gnomad EAS exome AF: 0.639

Gnomad FIN exome AF: 0.385

Gnomad NFE exome AF: 0.424

Gnomad OTH exome AF: 0.434

GnomAD4 exome AF: 0.426 AC: 622857 AN: 1461798 Hom.: 135631 Cov.: 57 AF XY: 0.429 AC XY: 311817 AN XY: 727210

African (AFR) AF: 0.291 AC: 9726 AN: 33480

American (AMR) AF: 0.263 AC: 11751 AN: 44710

Ashkenazi Jewish (ASJ) AF: 0.574 AC: 14995 AN: 26134

East Asian (EAS) AF: 0.625 AC: 24801 AN: 39700

South Asian (SAS) AF: 0.482 AC: 41614 AN: 86256

European-Finnish (FIN) AF: 0.387 AC: 20667 AN: 53404

Middle Eastern (MID) AF: 0.461 AC: 2661 AN: 5766

European-Non Finnish (NFE) AF: 0.423 AC: 470084 AN: 1111956

Other (OTH) AF: 0.440 AC: 26558 AN: 60392

GnomAD4 genome AF: 0.390 AC: 59299 AN: 151956 Hom.: 12160 Cov.: 31 AF XY: 0.392 AC XY: 29121 AN XY: 74266

African (AFR) AF: 0.297 AC: 12319 AN: 41470

American (AMR) AF: 0.329 AC: 5015 AN: 15252

Ashkenazi Jewish (ASJ) AF: 0.557 AC: 1933 AN: 3470

East Asian (EAS) AF: 0.643 AC: 3314 AN: 5154

South Asian (SAS) AF: 0.495 AC: 2382 AN: 4816

European-Finnish (FIN) AF: 0.393 AC: 4141 AN: 10546

Middle Eastern (MID) AF: 0.435 AC: 128 AN: 294

European-Non Finnish (NFE) AF: 0.423 AC: 28720 AN: 67938

Other (OTH) AF: 0.429 AC: 905 AN: 2108

Alfa AF: 0.423 Hom.: 69062

Bravo AF: 0.381

TwinsUK AF: 0.421 AC: 1560

ALSPAC AF: 0.431 AC: 1662

ESP6500AA AF: 0.297 AC: 1307

ESP6500EA AF: 0.433 AC: 3723

ExAC AF: 0.421 AC: 51147

Asia WGS AF: 0.534 AC: 1859 AN: 3478

EpiCase AF: 0.445

EpiControl AF: 0.438

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	6	not specified (6)
-	-	2	DPAGT1-congenital disorder of glycosylation (2)
-	-	1	Acute intermittent porphyria (1)
-	-	1	Congenital disorder of glycosylation (1)
-	-	1	Congenital myasthenic syndrome 13 (1)
-	-	1	DPAGT1-congenital disorder of glycosylation;C3553645:Congenital myasthenic syndrome 13 (1)
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.056
BayesDel_addAF	Benign	-0.61	T
BayesDel_noAF	Benign	-0.50
CADD	Benign	0.29
DANN	Benign	0.38
DEOGEN2	Benign	0.18	T
Eigen	Benign	-2.0
Eigen_PC	Benign	-2.0
FATHMM_MKL	Benign	0.026	N
LIST_S2	Benign	0.61	T
MetaRNN	Benign	0.0000076	T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	-0.17	N
PhyloP100		-0.57
PrimateAI	Benign	0.28	T
PROVEAN	Benign	-0.36	N
REVEL	Benign	0.20
Sift	Benign	0.55	T
Sift4G	Benign	0.53	T
Polyphen		0.0	B
Vest4		0.0040
MPC		0.42
ClinPred		0.0019	T
GERP RS		-4.2
RBP_binding_hub_radar		0.92
RBP_regulation_power_radar		2.0
Varity_R		0.027
gMVP		0.23
Mutation Taster		=89/11	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: rs643788; hg19: chr11-118967758; COSMIC: COSV53827927; COSMIC: COSV53827927;