rs10916846

Variant names:

• chr1-20660064-T-C
• rs10916846
• NM_005216.5:c.265+817A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_005216.5(DDOST):​c.265+817A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0666 in 152,170 control chromosomes in the GnomAD database, including 357 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.067 (357 hom., cov: 32)
• Consequence: DDOST NM_005216.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.21
• Publications: 3 publications found

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]

DDOST Gene-Disease associations (from GenCC):

• DDOST-congenital disorder of glycosylation

  Inheritance: AR Classification: DEFINITIVE, MODERATE, SUPPORTIVE, LIMITED Submitted by: Orphanet, Labcorp Genetics (formerly Invitae), G2P, PanelApp Australia, ClinGen

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.074 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DDOST	NM_005216.5	c.265+817A>G		intron_variant	Intron 2 of 10	ENST00000602624.7	NP_005207.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DDOST	ENST00000602624.7	c.265+817A>G		intron_variant	Intron 2 of 10	1	NM_005216.5	ENSP00000473655.2
DDOST	ENST00000415136.6	c.316+817A>G		intron_variant	Intron 2 of 10	1		ENSP00000399457.3
DDOST	ENST00000464364.1	c.265+817A>G		intron_variant	Intron 2 of 3	5		ENSP00000475634.1

Frequencies

GnomAD3 genomes AF: 0.0667 AC: 10143 AN: 152052 Hom.: 356 Cov.: 32

Gnomad AFR AF: 0.0655

Gnomad AMI AF: 0.0976

Gnomad AMR AF: 0.0682

Gnomad ASJ AF: 0.0840

Gnomad EAS AF: 0.0500

Gnomad SAS AF: 0.0808

Gnomad FIN AF: 0.0743

Gnomad MID AF: 0.0665

Gnomad NFE AF: 0.0649

Gnomad OTH AF: 0.0684

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0666 AC: 10142 AN: 152170 Hom.: 357 Cov.: 32 AF XY: 0.0675 AC XY: 5021 AN XY: 74406

African (AFR) AF: 0.0653 AC: 2712 AN: 41502

American (AMR) AF: 0.0681 AC: 1041 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.0840 AC: 291 AN: 3466

East Asian (EAS) AF: 0.0505 AC: 262 AN: 5190

South Asian (SAS) AF: 0.0806 AC: 389 AN: 4824

European-Finnish (FIN) AF: 0.0743 AC: 786 AN: 10576

Middle Eastern (MID) AF: 0.0646 AC: 19 AN: 294

European-Non Finnish (NFE) AF: 0.0649 AC: 4411 AN: 67998

Other (OTH) AF: 0.0672 AC: 142 AN: 2114

Alfa AF: 0.0673 Hom.: 616

Bravo AF: 0.0675

Asia WGS AF: 0.0530 AC: 186 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	3.2
DANN	Benign	0.72
PhyloP100		-1.2
Mutation Taster		=100/0	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: rs10916846; hg19: chr1-20986557;