chrX-75478990-AAT-AAT

Variant names:

• chrX-75478991-A-A
• NM_144969.3:c.

Variant summary

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

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. 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: -0.839
• 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 2 ACMG points.

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

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.: 19

GnomAD4 genome Cov.: 22

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		-0.84

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-74698826;