1-26469069-C-G

Variant names:

• chr1-26469069-C-G
• rs1553124038
• NM_205861.3:c.940C>G

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_205861.3(DHDDS):​c.940C>G​(p.Leu314Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,312 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. L314L) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: DHDDS NM_205861.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.69
• Publications: 0 publications found

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-AS1 (HGNC:40925): (DHDDS antisense RNA 1)

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.32153258).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_205861.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DHDDS	NM_205861.3	MANE Select	c.940C>G	p.Leu314Val	missense	Exon 9 of 9	NP_995583.1	Q86SQ9-1
	DHDDS	NM_024887.4		c.943C>G	p.Leu315Val	missense	Exon 9 of 9	NP_079163.2
	DHDDS	NM_001243564.2		c.838C>G	p.Leu280Val	missense	Exon 8 of 8	NP_001230493.1	Q86SQ9-4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DHDDS	ENST00000236342.12	TSL:1 MANE Select	c.940C>G	p.Leu314Val	missense	Exon 9 of 9	ENSP00000236342.7	Q86SQ9-1
	DHDDS	ENST00000526219.5	TSL:1	c.823C>G	p.Leu275Val	missense	Exon 8 of 8	ENSP00000434219.1	Q86SQ9-3
	DHDDS	ENST00000434391.6	TSL:1	n.*741C>G		non_coding_transcript_exon	Exon 9 of 9	ENSP00000403529.2	Q5T0A0

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1461312 Hom.: 0 Cov.: 34 AF XY: 0.00 AC XY: 0 AN XY: 726940

African (AFR) AF: 0.00 AC: 0 AN: 33462

American (AMR) AF: 0.00 AC: 0 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86224

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53344

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5374

European-Non Finnish (NFE) AF: 0.00000180 AC: 2 AN: 1112006

Other (OTH) AF: 0.00 AC: 0 AN: 60342

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.057	T
BayesDel_noAF	Benign	-0.32
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.34	T
Eigen	Uncertain	0.48
Eigen_PC	Uncertain	0.50
FATHMM_MKL	Uncertain	0.92	D
LIST_S2	Uncertain	0.88	D
M_CAP	Benign	0.017	T
MetaRNN	Benign	0.32	T
MetaSVM	Benign	-0.79	T
MutationAssessor	Benign	1.5	L
PhyloP100		2.7
PrimateAI	Uncertain	0.72	T
PROVEAN	Benign	-1.5	N
REVEL	Benign	0.13
Sift	Uncertain	0.0050	D
Sift4G	Uncertain	0.012	D
Polyphen		0.94	P
Vest4		0.33
MutPred		0.36		Gain of MoRF binding (P = 0.0972)
MVP		0.33
MPC		0.74
ClinPred		0.79	D
GERP RS		4.6
Varity_R		0.25
gMVP		0.57
Mutation Taster		=53/47	polymorphism

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

Other links and lift over

dbSNP: rs1553124038; hg19: chr1-26795560;