rs537816

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

• chr1-20661380-G-A
• chr1-20661380-G-C
• chr1-20661380-G-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The ENST00000415136.6(DDOST):​c.22C>T​(p.Arg8Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000274 in 1,459,266 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R8G) has been classified as Benign.

• Frequency:
  • Genomes: not found (cov: 35)
  • Exomes 𝑓: 0.0000027 (0 hom.)
• Consequence: DDOST ENST00000415136.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.184

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.08827612).

Transcripts

RefSeq

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

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DDOST	ENST00000602624.7	c.-30C>T		upstream_gene_variant		1	NM_005216.5	ENSP00000473655.2

Frequencies

GnomAD3 genomes Cov.: 35

GnomAD4 exome AF: 0.00000274 AC: 4 AN: 1459266 Hom.: 0 Cov.: 47 AF XY: 0.00000413 AC XY: 3 AN XY: 725890

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000116

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000270

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 35

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.29
BayesDel_addAF	Benign	-0.16	T
BayesDel_noAF	Benign	-0.47
CADD	Benign	17
DANN	Uncertain	0.99
DEOGEN2	Benign	0.071	T;T
Eigen	Benign	-0.74
Eigen_PC	Benign	-0.61
FATHMM_MKL	Benign	0.44	N
LIST_S2	Benign	0.40	T;.
M_CAP	Benign	0.0071	T
MetaRNN	Benign	0.088	T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.0	N;N
PrimateAI	Uncertain	0.49	T
PROVEAN	Benign	-0.040	N;N
REVEL	Benign	0.071
Sift	Benign	0.045	D;D
Sift4G	Benign	0.071	T;T
Polyphen		0.018	B;B
Vest4		0.17
MutPred		0.41		Loss of MoRF binding (P = 0.0073);Loss of MoRF binding (P = 0.0073);
MVP		0.56
MPC		0.30
ClinPred		0.58	D
GERP RS		3.4
Varity_R		0.081
gMVP		0.67

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: rs537816; hg19: chr1-20987873;