11-119096571-A-C

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_Moderate BP6 BS1 BS2

The NM_001382.4(DPAGT1):c.*427T>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00904 in 289,840 control chromosomes in the GnomAD database, including 42 homozygotes. 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 0.013 (37 hom., cov: 32)
  • Exomes 𝑓: 0.0046 (5 hom.)
• Consequence: DPAGT1 NM_001382.4 3_prime_UTR
• Clinical Significance: Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1 B:3
• Conservation: PhyloP100: 2.48

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 Benign. Variant got -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.23).
• BP6: Variant 11-119096571-A-C is Benign according to our data. Variant chr11-119096571-A-C is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 302740.We mark this variant Likely_benign, oryginal submissions are: {Likely_benign=3, Uncertain_significance=1}.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0131 (1991/152290) while in subpopulation AFR AF= 0.0364 (1510/41538). AF 95% confidence interval is 0.0348. There are 37 homozygotes in gnomad4. There are 947 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 35 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DPAGT1	NM_001382.4	c.*427T>G		3_prime_UTR_variant	9/9	ENST00000354202.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DPAGT1	ENST00000354202.9	c.*427T>G		3_prime_UTR_variant	9/9	1	NM_001382.4	P1

Frequencies

GnomAD3 genomes AF: 0.0130 AC: 1974 AN: 152172 Hom.: 35 Cov.: 32

Gnomad AFR AF: 0.0360

Gnomad AMI AF: 0.00110

Gnomad AMR AF: 0.00550

Gnomad ASJ AF: 0.00375

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00124

Gnomad FIN AF: 0.00207

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.00495

Gnomad OTH AF: 0.00813

GnomAD4 exome AF: 0.00457 AC: 629 AN: 137550 Hom.: 5 Cov.: 0 AF XY: 0.00393 AC XY: 289 AN XY: 73560

Gnomad4 AFR exome AF: 0.0374

Gnomad4 AMR exome AF: 0.00368

Gnomad4 ASJ exome AF: 0.00365

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00144

Gnomad4 FIN exome AF: 0.00421

Gnomad4 NFE exome AF: 0.00414

Gnomad4 OTH exome AF: 0.00498

GnomAD4 genome AF: 0.0131 AC: 1991 AN: 152290 Hom.: 37 Cov.: 32 AF XY: 0.0127 AC XY: 947 AN XY: 74476

Gnomad4 AFR AF: 0.0364

Gnomad4 AMR AF: 0.00549

Gnomad4 ASJ AF: 0.00375

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00124

Gnomad4 FIN AF: 0.00207

Gnomad4 NFE AF: 0.00495

Gnomad4 OTH AF: 0.00804

Alfa AF: 0.00707 Hom.: 8

Bravo AF: 0.0145

Asia WGS AF: 0.00260 AC: 9 AN: 3478

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:1 Benign:3

Revision: criteria provided, conflicting classifications

Submissions by phenotype

Congenital disorder of glycosylation Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Acute intermittent porphyria Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

DPAGT1-congenital disorder of glycosylation Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 12, 2018

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease. -

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

May 24, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.23
Cadd	Benign	11
Dann	Benign	0.82

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

Publications

LitVar

Other links and lift over

dbSNP: rs28990975; hg19: chr11-118967281;