1-20661380-G-C

Variant names:

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The ENST00000415136.6(DDOST):c.22C>G(p.Arg8Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.996 in 1,611,616 control chromosomes in the GnomAD database, including 799,010 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in UniProt.

Frequency

Genomes: 𝑓 0.98 ( 72873 hom., cov: 35)

Exomes 𝑓: 1.0 ( 726137 hom. )

Consequence

DDOST
ENST00000415136.6 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.184

Variant links:

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 links:

KIF17 (HGNC:19167): (kinesin family member 17) Predicted to enable microtubule binding activity and plus-end-directed microtubule motor activity. Predicted to be involved in anterograde dendritic transport of neurotransmitter receptor complex and cell projection organization. Predicted to act upstream of or within microtubule-based process; protein-containing complex localization; and vesicle-mediated transport. Predicted to be located in microtubule cytoskeleton. Predicted to be part of intraciliary transport particle B and kinesin complex. Predicted to be active in cilium; microtubule cytoskeleton; and neuron projection. [provided by Alliance of Genome Resources, Apr 2022]

KIF17 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=8.923681E-7).

BP6

Variant 1-20661380-G-C is Benign according to our data. Variant chr1-20661380-G-C is described in ClinVar as [Benign]. Clinvar id is 1164173.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.993 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DDOST	NM_005216.5 link	c.-30C>G		upstream_gene_variant		ENST00000602624.7	NP_005207.3	P39656A0A024RAD5
KIF17	XR_007062426.1 link	n.*250C>G		downstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
DDOST	ENST00000415136.6 link	c.22C>G	p.Arg8Gly	missense_variant	Exon 1 of 11	1		ENSP00000399457.3	P39656-1
DDOST	ENST00000464364.1 link	c.-30C>G		5_prime_UTR_variant	Exon 1 of 4	5		ENSP00000475634.1	U3KQ84
DDOST	ENST00000602624.7 link	c.-30C>G		upstream_gene_variant		1	NM_005216.5	ENSP00000473655.2	A0A0C4DGS1
DDOST	ENST00000477229.1 link	n.-11C>G		upstream_gene_variant		2

Frequencies

GnomAD3 genomes

AF:

0.977

AC:

148798

AN:

152236

Hom.:

72820

Cov.:

show subpopulations

Gnomad AFR

AF:

0.922

Gnomad AMI

AF:

1.00

Gnomad AMR

AF:

0.991

Gnomad ASJ

AF:

1.00

Gnomad EAS

AF:

1.00

Gnomad SAS

AF:

1.00

Gnomad FIN

AF:

1.00

Gnomad MID

AF:

1.00

Gnomad NFE

AF:

1.00

Gnomad OTH

AF:

0.983

GnomAD3 exomes

AF:

0.994

AC:

240691

AN:

242152

Hom.:

119679

AF XY:

0.996

AC XY:

131790

AN XY:

132384

show subpopulations

Gnomad AFR exome

AF:

0.919

Gnomad AMR exome

AF:

0.994

Gnomad ASJ exome

AF:

1.00

Gnomad EAS exome

AF:

1.00

Gnomad SAS exome

AF:

1.00

Gnomad FIN exome

AF:

1.00

Gnomad NFE exome

AF:

1.00

Gnomad OTH exome

AF:

0.997

GnomAD4 exome

AF:

0.998

AC:

1455644

AN:

1459262

Hom.:

726137

Cov.:

AF XY:

0.998

AC XY:

724363

AN XY:

725888

show subpopulations

Gnomad4 AFR exome

AF:

0.917

Gnomad4 AMR exome

AF:

0.995

Gnomad4 ASJ exome

AF:

1.00

Gnomad4 EAS exome

AF:

1.00

Gnomad4 SAS exome

AF:

1.00

Gnomad4 FIN exome

AF:

1.00

Gnomad4 NFE exome

AF:

1.00

Gnomad4 OTH exome

AF:

0.995

GnomAD4 genome

AF:

0.977

AC:

148909

AN:

152354

Hom.:

72873

Cov.:

AF XY:

0.979

AC XY:

72924

AN XY:

74502

show subpopulations

Gnomad4 AFR

AF:

0.922

Gnomad4 AMR

AF:

0.991

Gnomad4 ASJ

AF:

1.00

Gnomad4 EAS

AF:

1.00

Gnomad4 SAS

AF:

1.00

Gnomad4 FIN

AF:

1.00

Gnomad4 NFE

AF:

1.00

Gnomad4 OTH

AF:

0.983

Alfa

AF:

0.892

Hom.:

21837

Bravo

AF:

0.974

TwinsUK

AF:

0.999

AC:

3705

ALSPAC

AF:

1.00

AC:

3853

ESP6500AA

AF:

0.926

AC:

4049

ESP6500EA

AF:

1.00

AC:

8543

ExAC

AF:

0.992

AC:

119918

Asia WGS

AF:

0.997

AC:

3466

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Congenital disorder of glycosylation type Ir

Benign:1

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not provided

Benign:1

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.064

BayesDel_addAF

Benign

-0.59

BayesDel_noAF

Benign

-0.57

CADD

Benign

DANN

Benign

0.91

DEOGEN2

Benign

0.071

T;T

Eigen

Benign

-0.96

Eigen_PC

Benign

-0.79

FATHMM_MKL

Benign

0.080

LIST_S2

Benign

0.21

T;.

MetaRNN

Benign

8.9e-7

T;T

MetaSVM

Benign

-0.92

MutationAssessor

Benign

0.0

N;N

PrimateAI

Benign

0.44

PROVEAN

Benign

0.010

N;N

REVEL

Benign

0.070

Sift

Benign

1.0

T;T

Sift4G

Benign

0.59

T;T

Polyphen

0.0

B;B

Vest4

0.056

MPC

0.27

ClinPred

0.017

GERP RS

3.4

Varity_R

0.079

gMVP

0.72

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over