chr1-26469069-C-T

Variant names:

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

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Moderate BP6_Moderate BP7

The NM_205861.3(DHDDS):​c.940C>T​(p.Leu314Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000205 in 1,461,312 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 (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: DHDDS NM_205861.3 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• 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: Likely_benign. The variant received -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.39).
• BP6: Variant 1-26469069-C-T is Benign according to our data. Variant chr1-26469069-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 471783.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=2.69 with no splicing effect.

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>T	p.Leu314Leu	synonymous	Exon 9 of 9	NP_995583.1	Q86SQ9-1
	DHDDS	NM_024887.4		c.943C>T	p.Leu315Leu	synonymous	Exon 9 of 9	NP_079163.2
	DHDDS	NM_001243564.2		c.838C>T	p.Leu280Leu	synonymous	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>T	p.Leu314Leu	synonymous	Exon 9 of 9	ENSP00000236342.7	Q86SQ9-1
	DHDDS	ENST00000526219.5	TSL:1	c.823C>T	p.Leu275Leu	synonymous	Exon 8 of 8	ENSP00000434219.1	Q86SQ9-3
	DHDDS	ENST00000434391.6	TSL:1	n.*741C>T		non_coding_transcript_exon	Exon 9 of 9	ENSP00000403529.2	Q5T0A0

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000205 AC: 3 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: 0.00000270 AC: 3 AN: 1112006

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

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	Retinitis pigmentosa 59 (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.39
CADD	Benign	12
DANN	Benign	0.94
PhyloP100		2.7
Mutation Taster		=88/12	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;