ENST00000434391.6:n.-143C>T

Variant names:

• chr1-26432139-C-T
• ENST00000746087.1:n.158G>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The ENST00000434391.6(DHDDS):​n.-293C>T variant causes a upstream gene change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 34)
• Consequence: DHDDS ENST00000434391.6 upstream_gene
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.378
• Publications: 0 publications found

Genes affected

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

LOC124903883 (HGNC:):

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 Gene-Disease associations (from GenCC):

• DHDDS-CDG

  Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
• retinitis pigmentosa 59

  Inheritance: AR Classification: DEFINITIVE, LIMITED Submitted by: G2P, Labcorp Genetics (formerly Invitae)
• developmental delay and seizures with or without movement abnormalities

  Inheritance: AD Classification: STRONG Submitted by: G2P, Labcorp Genetics (formerly Invitae)
• retinitis pigmentosa

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• undetermined early-onset epileptic encephalopathy

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000434391.6. 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.-293C>T		upstream_gene	N/A	NP_995583.1	Q86SQ9-1
	DHDDS	NM_024887.4		c.-293C>T		upstream_gene	N/A	NP_079163.2
	DHDDS	NM_001243564.2		c.-293C>T		upstream_gene	N/A	NP_001230493.1	Q86SQ9-4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DHDDS-AS1	ENST00000746087.1		n.158G>A		non_coding_transcript_exon	Exon 1 of 2
	DHDDS-AS1	ENST00000746088.1		n.122G>A		non_coding_transcript_exon	Exon 1 of 3
	DHDDS-AS1	ENST00000746089.1		n.85G>A		non_coding_transcript_exon	Exon 1 of 2

Frequencies

GnomAD3 genomes Cov.: 34

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 34

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	5.7
DANN	Benign	0.89
PhyloP100		-0.38
PromoterAI		0.14	Neutral

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

hg19: chr1-26758630;