DKC1 p.Ala439Ala

Variant names:

• chrX-154775249-T-T
• ENST00000369550.10:c.

Your query was ambiguous. Multiple possible variants found:

• chrX-154775250--
• chrX-154775252-C-T
• chrX-154775252-C-A
• chrX-154775252-C-G

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_001363.5(DKC1):​c. variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 24)
• Consequence: DKC1 NM_001363.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.304
• Publications: 0 publications found

Genes affected

DKC1 (HGNC:2890): (dyskerin pseudouridine synthase 1) This gene functions in two distinct complexes. It plays an active role in telomerase stabilization and maintenance, as well as recognition of snoRNAs containing H/ACA sequences which provides stability during biogenesis and assembly into H/ACA small nucleolar RNA ribonucleoproteins (snoRNPs). This gene is highly conserved and widely expressed, and may play additional roles in nucleo-cytoplasmic shuttling, DNA damage response, and cell adhesion. Mutations have been associated with X-linked dyskeratosis congenita. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jan 2014]

SNORA56 (HGNC:32650): (small nucleolar RNA, H/ACA box 56) Biosynthesis of stable cellular RNAs such as tRNAs, rRNAs, snRNAs, and snoRNAs is aided by covalent nucleotide modification after transcription. The modified nucleotides are involved in correct RNA folding, establishment of correct RNA-RNA and RNA-protein interactions, and in the correct function of mature RNAs. The RNA encoded by this gene is thought to mediate the pseudouridylation of residue U1664 of 28S rRNA. [provided by RefSeq, Feb 2009]

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001363.5. 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
	DKC1	NM_001363.5	MANE Select	c.		intron	N/A	NP_001354.1	O60832-1
	DKC1	NM_001288747.2		c.		exon_region	Exon 12 of 14	NP_001275676.1	O60832-2
	DKC1	NM_001288747.2		c.		3_prime_UTR	Exon 12 of 14	NP_001275676.1	O60832-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DKC1	ENST00000369550.10	TSL:1 MANE Select	c.		exon_region	Exon 15 of 15	ENSP00000358563.5	O60832-1
	DKC1	ENST00000369550.10	TSL:1 MANE Select	c.		3_prime_UTR	Exon 15 of 15	ENSP00000358563.5	O60832-1
	DKC1	ENST00000620277.4	TSL:1	n.		exon_region	Exon 14 of 14

Frequencies

GnomAD3 genomes Cov.: 24

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 24

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.30

Splicing

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chrX-154003524;