Variant 1-26432985-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3

The NM_205861.3(DHDDS):c.40C>T(p.Arg14Trp) 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 1,461,878 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 31)

Exomes 𝑓: 0.0000027 ( 0 hom. )

Consequence

DHDDS
NM_205861.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.30

Variant links:

Genes affected

DHDDS (HGNC:20603): (dehydrodolichyl diphosphate synthase subunit) The protein encoded by this gene catalyzes cis-prenyl chain elongation to produce the polyprenyl backbone of dolichol, a glycosyl carrier lipid required for the biosynthesis of several classes of glycoproteins. Mutations in this gene are associated with retinitis pigmentosa type 59. Alternatively spliced transcript variants encoding different isoforms have been described for this gene. [provided by RefSeq, Aug 2011]

DHDDS links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.749

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DHDDS	NM_205861.3 linkuse as main transcript	c.40C>T	p.Arg14Trp	missense_variant	2/9	ENST00000236342.12	NP_995583.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DHDDS	ENST00000236342.12 linkuse as main transcript	c.40C>T	p.Arg14Trp	missense_variant	2/9	1	NM_205861.3	ENSP00000236342	P4	Q86SQ9-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000274

AC:

AN:

1461878

Hom.:

Cov.:

AF XY:

0.00000275

AC XY:

AN XY:

727238

show subpopulations

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:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000360

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Revvity Omics, Revvity

May 25, 2022

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.16

BayesDel_addAF

Pathogenic

0.24

BayesDel_noAF

Uncertain

0.11

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.35

T;.;D;.;.;.;T;T;.;T;T;.;.;.

Eigen

Uncertain

0.25

Eigen_PC

Uncertain

0.31

FATHMM_MKL

Uncertain

0.76

LIST_S2

Uncertain

0.93

D;D;D;D;D;D;D;D;D;D;D;D;D;D

M_CAP

Benign

0.059

MetaRNN

Pathogenic

0.75

D;D;D;D;D;D;D;D;D;D;D;D;D;D

MetaSVM

Benign

-0.50

MutationAssessor

Uncertain

2.2

.;M;M;M;.;M;.;.;.;.;.;.;.;.

MutationTaster

Benign

1.0

D;D;D;D;D;D

PrimateAI

Uncertain

0.48

PROVEAN

Pathogenic

-5.3

D;D;D;D;D;D;D;D;D;D;D;D;D;D

REVEL

Uncertain

0.42

Sift

Uncertain

0.0030

D;D;D;D;D;D;D;T;T;D;T;D;D;T

Sift4G

Uncertain

0.056

T;D;D;D;T;D;T;T;T;D;T;D;D;T

Polyphen

0.35, 1.0, 0.48

.;.;B;D;.;P;.;.;.;.;.;.;.;.

Vest4

0.25

MutPred

0.59

Loss of MoRF binding (P = 0.0875);Loss of MoRF binding (P = 0.0875);Loss of MoRF binding (P = 0.0875);Loss of MoRF binding (P = 0.0875);Loss of MoRF binding (P = 0.0875);Loss of MoRF binding (P = 0.0875);Loss of MoRF binding (P = 0.0875);Loss of MoRF binding (P = 0.0875);Loss of MoRF binding (P = 0.0875);Loss of MoRF binding (P = 0.0875);Loss of MoRF binding (P = 0.0875);Loss of MoRF binding (P = 0.0875);Loss of MoRF binding (P = 0.0875);Loss of MoRF binding (P = 0.0875);

MVP

0.53

MPC

0.52

ClinPred

0.98

GERP RS

4.8

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.66

gMVP

0.78

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

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over