X-75478992-T-TAA

Variant names:

• chrX-75478990-AAT-AAT
• NM_144969.3:c.

Variant summary

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

The NM_144969.3(ZDHHC15):​c. variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. It is difficult to determine the true allele frequency of this variant because it is of type MNV, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 22)
• Consequence: ZDHHC15 NM_144969.3 splice_region, intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.835
• Publications: 0 publications found

Genes affected

ZDHHC15 (HGNC:20342): (zinc finger DHHC-type palmitoyltransferase 15) The protein encoded by this gene belongs to the DHHC palmitoyltransferase family. Mutations in this gene are associated with mental retardatio X-linked type 91 (MRX91). Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Sep 2009]

ZDHHC15 Gene-Disease associations (from GenCC):

• intellectual disability, X-linked 91

  Inheritance: XL, Unknown Classification: LIMITED Submitted by: G2P, Labcorp Genetics (formerly Invitae)
• X-linked complex neurodevelopmental disorder

  Inheritance: XL Classification: NO_KNOWN Submitted by: ClinGen

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_144969.3. 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
	ZDHHC15	NM_144969.3	MANE Select	c.		splice_region intron	N/A	NP_659406.1	Q96MV8-1
	ZDHHC15	NM_001146256.2		c.		splice_region intron	N/A	NP_001139728.1	Q96MV8-3
	ZDHHC15	NM_001146257.2		c.		splice_region intron	N/A	NP_001139729.1	Q96MV8-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZDHHC15	ENST00000373367.8	TSL:1 MANE Select	c.		splice_region intron	N/A	ENSP00000362465.3	Q96MV8-1
	ZDHHC15	ENST00000858993.1		c.		splice_region intron	N/A	ENSP00000529052.1
	ZDHHC15	ENST00000858994.1		c.		splice_region intron	N/A	ENSP00000529053.1

Frequencies

GnomAD3 genomes Cov.: 22

GnomAD4 exome Cov.: 18

GnomAD4 genome Cov.: 22

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		-0.83

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-74698825;