1-20652339-T-C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_005216.5(DDOST):c.*40A>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 0.87 in 1,529,674 control chromosomes in the GnomAD database, including 579,708 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.84 (53971 hom., cov: 32)
  • Exomes 𝑓: 0.87 (525737 hom.)
• Consequence: DDOST NM_005216.5 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: -3.10

Genes affected

DDOST (HGNC:2728): (dolichyl-diphosphooligosaccharide--protein glycosyltransferase non-catalytic subunit) This gene encodes a component of the oligosaccharyltransferase complex which catalyzes the transfer of high-mannose oligosaccharides to asparagine residues on nascent polypeptides in the lumen of the rough endoplasmic reticulum. The protein complex co-purifies with ribosomes. The product of this gene is also implicated in the processing of advanced glycation endproducts (AGEs), which form from non-enzymatic reactions between sugars and proteins or lipids and are associated with aging and hyperglycemia. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BP6: Variant 1-20652339-T-C is Benign according to our data. Variant chr1-20652339-T-C is described in ClinVar as [Benign]. Clinvar id is 295057.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.873 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DDOST	NM_005216.5	c.*40A>G		3_prime_UTR_variant	11/11	ENST00000602624.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DDOST	ENST00000602624.7	c.*40A>G		3_prime_UTR_variant	11/11	1	NM_005216.5	P1
DDOST	ENST00000415136.6	c.*40A>G		3_prime_UTR_variant	11/11	1

Frequencies

GnomAD3 genomes AF: 0.840 AC: 127779 AN: 152052 Hom.: 53937 Cov.: 32

Gnomad AFR AF: 0.764

Gnomad AMI AF: 0.837

Gnomad AMR AF: 0.811

Gnomad ASJ AF: 0.903

Gnomad EAS AF: 0.809

Gnomad SAS AF: 0.886

Gnomad FIN AF: 0.904

Gnomad MID AF: 0.902

Gnomad NFE AF: 0.878

Gnomad OTH AF: 0.866

GnomAD3 exomes AF: 0.862 AC: 145250 AN: 168494 Hom.: 62788 AF XY: 0.867 AC XY: 78655 AN XY: 90736

Gnomad AFR exome AF: 0.769

Gnomad AMR exome AF: 0.808

Gnomad ASJ exome AF: 0.902

Gnomad EAS exome AF: 0.822

Gnomad SAS exome AF: 0.888

Gnomad FIN exome AF: 0.910

Gnomad NFE exome AF: 0.879

Gnomad OTH exome AF: 0.875

GnomAD4 exome AF: 0.873 AC: 1202625 AN: 1377504 Hom.: 525737 Cov.: 30 AF XY: 0.874 AC XY: 592512 AN XY: 678126

Gnomad4 AFR exome AF: 0.754

Gnomad4 AMR exome AF: 0.806

Gnomad4 ASJ exome AF: 0.901

Gnomad4 EAS exome AF: 0.799

Gnomad4 SAS exome AF: 0.885

Gnomad4 FIN exome AF: 0.909

Gnomad4 NFE exome AF: 0.878

Gnomad4 OTH exome AF: 0.873

GnomAD4 genome AF: 0.840 AC: 127870 AN: 152170 Hom.: 53971 Cov.: 32 AF XY: 0.842 AC XY: 62626 AN XY: 74410

Gnomad4 AFR AF: 0.764

Gnomad4 AMR AF: 0.811

Gnomad4 ASJ AF: 0.903

Gnomad4 EAS AF: 0.808

Gnomad4 SAS AF: 0.886

Gnomad4 FIN AF: 0.904

Gnomad4 NFE AF: 0.879

Gnomad4 OTH AF: 0.867

Alfa AF: 0.865 Hom.: 16599

Bravo AF: 0.830

Asia WGS AF: 0.839 AC: 2916 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Congenital disorder of glycosylation type Ir Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 30, 2021

- -

Congenital disorder of glycosylation Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Parkinson Disease, Recessive Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 23, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
Cadd	Benign	1.6
Dann	Benign	0.29
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs6893; hg19: chr1-20978832;