rs142000757
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Variant summary
Our verdict is Benign. Variant got -11 ACMG points: 2P and 13B. PM2BP4_StrongBP6_Very_StrongBP7
The NM_014908.4(DOLK):āc.114A>Gā(p.Val38=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000806 in 1,613,028 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (ā ā ).
Frequency
Genomes: š 0.000026 ( 0 hom., cov: 31)
Exomes š: 0.0000062 ( 0 hom. )
Consequence
DOLK
NM_014908.4 synonymous
NM_014908.4 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.230
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]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -11 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.67).
BP6
?
Variant 9-128947190-T-C is Benign according to our data. Variant chr9-128947190-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 532852.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
?
Synonymous conserved (PhyloP=-0.23 with no splicing effect.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
DOLK | NM_014908.4 | c.114A>G | p.Val38= | synonymous_variant | 1/1 | ENST00000372586.4 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
DOLK | ENST00000372586.4 | c.114A>G | p.Val38= | synonymous_variant | 1/1 | NM_014908.4 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000263 AC: 4AN: 152070Hom.: 0 Cov.: 31
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GnomAD4 exome AF: 0.00000616 AC: 9AN: 1460958Hom.: 0 Cov.: 31 AF XY: 0.00000825 AC XY: 6AN XY: 726832
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GnomAD4 genome ? AF: 0.0000263 AC: 4AN: 152070Hom.: 0 Cov.: 31 AF XY: 0.0000269 AC XY: 2AN XY: 74282
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ClinVar
Significance: Likely benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
DK1-congenital disorder of glycosylation Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Sep 19, 2023 | - - |
Cardiovascular phenotype Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Aug 14, 2019 | This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. - |
Computational scores
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Name
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
RBP_binding_hub_radar
RBP_regulation_power_radar
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at