rs1554826859

Variant names:

• chr9-128947167-G-A
• rs1554826859
• NM_014908.4:c.137C>T

Your query was ambiguous. Multiple possible variants found:

• chr9-128947167-G-A
• chr9-128947167-G-C

Variant summary

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

The NM_014908.4(DOLK):​c.137C>T​(p.Ala46Val) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 31)
• Consequence: DOLK NM_014908.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.11

Genes affected

DOLK (HGNC:23406): (dolichol kinase) The protein encoded by this gene catalyzes the CTP-mediated phosphorylation of dolichol, and is involved in the synthesis of Dol-P-Man, which is an essential glycosyl carrier lipid for C- and O-mannosylation, N- and O-linked glycosylation of proteins, and for the biosynthesis of glycosyl phosphatidylinositol anchors in endoplasmic reticulum. Mutations in this gene are associated with dolichol kinase deficiency.[provided by RefSeq, Apr 2010]

ENSG00000251184 (HGNC:):

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=0.2201246).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DOLK	NM_014908.4	c.137C>T	p.Ala46Val	missense_variant	Exon 1 of 1	ENST00000372586.4	NP_055723.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DOLK	ENST00000372586.4	c.137C>T	p.Ala46Val	missense_variant	Exon 1 of 1	6	NM_014908.4	ENSP00000361667.3
ENSG00000251184	ENST00000482796.1	c.39-2022G>A		intron_variant	Intron 1 of 4	2		ENSP00000417556.2

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 31

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

DK1-congenital disorder of glycosylation Uncertain:1

Feb 22, 2022

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated. ClinVar contains an entry for this variant (Variation ID: 532849). This variant has not been reported in the literature in individuals affected with DOLK-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces alanine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 46 of the DOLK protein (p.Ala46Val). -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Uncertain	0.047	T
BayesDel_noAF	Benign	-0.17
CADD	Uncertain	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.23	T
Eigen	Benign	-0.11
Eigen_PC	Benign	0.069
FATHMM_MKL	Benign	0.56	D
LIST_S2	Uncertain	0.89	D
M_CAP	Benign	0.034	D
MetaRNN	Benign	0.22	T
MetaSVM	Benign	-0.46	T
MutationAssessor	Benign	0.34	N
PrimateAI	Uncertain	0.53	T
PROVEAN	Benign	-0.14	N
REVEL	Benign	0.25
Sift	Uncertain	0.0090	D
Sift4G	Benign	0.14	T
Polyphen		0.0040	B
Vest4		0.34
MutPred		0.30		Loss of helix (P = 0.0558);
MVP		0.80
MPC		0.51
ClinPred		0.69	D
GERP RS		4.2
Varity_R		0.12
gMVP		0.47

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: rs1554826859; hg19: chr9-131709446;