chrX-75417613-A-G

Variant names:

• chrX-75417613-A-G
• rs2146767
• NM_144969.3:c.864-423T>C

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_144969.3(ZDHHC15):​c.864-423T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. 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: 𝑓 0.83 (28457 hom., 27738 hem., cov: 23)
  • Failed GnomAD Quality Control
• Consequence: ZDHHC15 NM_144969.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.720
• 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: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZDHHC15	NM_144969.3	c.864-423T>C		intron_variant	Intron 9 of 11	ENST00000373367.8	NP_659406.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZDHHC15	ENST00000373367.8	c.864-423T>C		intron_variant	Intron 9 of 11	1	NM_144969.3	ENSP00000362465.3
ZDHHC15	ENST00000541184.1	c.837-423T>C		intron_variant	Intron 8 of 10	2		ENSP00000445420.1

Frequencies

GnomAD3 genomes AF: 0.830 AC: 92061 AN: 110878 Hom.: 28471 Cov.: 23

Gnomad AFR AF: 0.483

Gnomad AMI AF: 1.00

Gnomad AMR AF: 0.928

Gnomad ASJ AF: 0.970

Gnomad EAS AF: 0.976

Gnomad SAS AF: 0.862

Gnomad FIN AF: 0.984

Gnomad MID AF: 0.954

Gnomad NFE AF: 0.972

Gnomad OTH AF: 0.869

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

GnomAD4 genome Data not reliable, filtered out with message: InbreedingCoeff AF: 0.830 AC: 92062 AN: 110934 Hom.: 28457 Cov.: 23 AF XY: 0.837 AC XY: 27738 AN XY: 33146

African (AFR) AF: 0.482 AC: 14721 AN: 30520

American (AMR) AF: 0.928 AC: 9583 AN: 10331

Ashkenazi Jewish (ASJ) AF: 0.970 AC: 2567 AN: 2646

East Asian (EAS) AF: 0.975 AC: 3417 AN: 3503

South Asian (SAS) AF: 0.861 AC: 2235 AN: 2596

European-Finnish (FIN) AF: 0.984 AC: 5824 AN: 5920

Middle Eastern (MID) AF: 0.949 AC: 205 AN: 216

European-Non Finnish (NFE) AF: 0.972 AC: 51507 AN: 53000

Other (OTH) AF: 0.869 AC: 1320 AN: 1519

Alfa AF: 0.912 Hom.: 15053

Bravo AF: 0.815

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	2.8
DANN	Benign	0.61
PhyloP100		0.72
Mutation Taster		=100/0	polymorphism (auto)

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: rs2146767; hg19: chrX-74637448;