ENST00000415136.6:c.22C>G

Variant names:

• chr1-20661380-G-C
• rs537816
• ENST00000415136.6:c.22C>G

Variant summary

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

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. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.98 (72873 hom., cov: 35)
  • Exomes 𝑓: 1.0 (726137 hom.)
• Consequence: DDOST ENST00000415136.6 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.184
• Publications: 27 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]

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 Gene-Disease associations (from GenCC):

• schizophrenia

  Inheritance: Unknown Classification: NO_KNOWN Submitted by: Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -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 VariationId 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000415136.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DDOST	NM_005216.5	MANE Select	c.-30C>G		upstream_gene	N/A	NP_005207.3

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DDOST	ENST00000415136.6	TSL:1	c.22C>G	p.Arg8Gly	missense	Exon 1 of 11	ENSP00000399457.3
	DDOST	ENST00000464364.1	TSL:5	c.-30C>G		5_prime_UTR	Exon 1 of 4	ENSP00000475634.1
	DDOST	ENST00000602624.7	TSL:1 MANE Select	c.-30C>G		upstream_gene	N/A	ENSP00000473655.2

Frequencies

GnomAD3 genomes AF: 0.977 AC: 148798 AN: 152236 Hom.: 72820 Cov.: 35

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

GnomAD2 exomes AF: 0.994 AC: 240691 AN: 242152 AF XY: 0.996

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 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.: 47 AF XY: 0.998 AC XY: 724363 AN XY: 725888

African (AFR) AF: 0.917 AC: 30640 AN: 33422

American (AMR) AF: 0.995 AC: 44285 AN: 44526

Ashkenazi Jewish (ASJ) AF: 1.00 AC: 26049 AN: 26054

East Asian (EAS) AF: 1.00 AC: 39612 AN: 39614

South Asian (SAS) AF: 1.00 AC: 85978 AN: 85986

European-Finnish (FIN) AF: 1.00 AC: 52341 AN: 52350

Middle Eastern (MID) AF: 0.997 AC: 5734 AN: 5754

European-Non Finnish (NFE) AF: 1.00 AC: 1111050 AN: 1111278

Other (OTH) AF: 0.995 AC: 59955 AN: 60278

GnomAD4 genome AF: 0.977 AC: 148909 AN: 152354 Hom.: 72873 Cov.: 35 AF XY: 0.979 AC XY: 72924 AN XY: 74502

African (AFR) AF: 0.922 AC: 38317 AN: 41566

American (AMR) AF: 0.991 AC: 15170 AN: 15312

Ashkenazi Jewish (ASJ) AF: 1.00 AC: 3472 AN: 3472

East Asian (EAS) AF: 1.00 AC: 5175 AN: 5176

South Asian (SAS) AF: 1.00 AC: 4832 AN: 4832

European-Finnish (FIN) AF: 1.00 AC: 10630 AN: 10630

Middle Eastern (MID) AF: 1.00 AC: 294 AN: 294

European-Non Finnish (NFE) AF: 1.00 AC: 68027 AN: 68044

Other (OTH) AF: 0.983 AC: 2080 AN: 2116

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

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	Congenital disorder of glycosylation type Ir (1)
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.064
BayesDel_addAF	Benign	-0.59	T
BayesDel_noAF	Benign	-0.57
CADD	Benign	17
DANN	Benign	0.91
DEOGEN2	Benign	0.071	T
Eigen	Benign	-0.96
Eigen_PC	Benign	-0.79
FATHMM_MKL	Benign	0.080	N
LIST_S2	Benign	0.21	T
MetaRNN	Benign	8.9e-7	T
MetaSVM	Benign	-0.92	T
MutationAssessor	Benign	0.0	N
PhyloP100		-0.18
PrimateAI	Benign	0.44	T
PROVEAN	Benign	0.010	N
REVEL	Benign	0.070
Sift	Benign	1.0	T
Sift4G	Benign	0.59	T
Polyphen		0.0	B
Vest4		0.056
MPC		0.27
ClinPred		0.017	T
GERP RS		3.4
PromoterAI		0.14	Neutral
Varity_R		0.079
gMVP		0.72
Mutation Taster		=298/2	polymorphism (auto)

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

Other links and lift over

dbSNP: rs537816; hg19: chr1-20987873; COSMIC: COSV56117446; COSMIC: COSV56117446;