rs797046116

Positions:

• chrX-75523015-C-T

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_Moderate BS2

The NM_144969.3(ZDHHC15):​c.10G>A​(p.Gly4Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000365 in 1,094,790 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 2 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 22)
  • Exomes 𝑓: 0.0000037 (0 hom. 2 hem.)
• Consequence: ZDHHC15 NM_144969.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.37

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]

ACMG classification

Verdict is Likely_benign. Variant got -6 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.12109193).
• BS2: High Hemizygotes in GnomAdExome4 at 2 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ZDHHC15	NM_144969.3	c.10G>A	p.Gly4Ser	missense_variant	1/12	ENST00000373367.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ZDHHC15	ENST00000373367.8	c.10G>A	p.Gly4Ser	missense_variant	1/12	1	NM_144969.3	P1
ZDHHC15	ENST00000541184.1	c.10G>A	p.Gly4Ser	missense_variant	1/11	2
ZDHHC15	ENST00000482827.1			upstream_gene_variant		5

Frequencies

GnomAD3 genomes Cov.: 22

GnomAD4 exome AF: 0.00000365 AC: 4 AN: 1094790 Hom.: 0 Cov.: 31 AF XY: 0.00000555 AC XY: 2 AN XY: 360430

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000476

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 22

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Genetic Services Laboratory, University of Chicago

Sep 26, 2014

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.15
BayesDel_addAF	Benign	-0.32	T
BayesDel_noAF	Benign	-0.70
CADD	Benign	16
DANN	Uncertain	0.99
DEOGEN2	Benign	0.087	T;.
FATHMM_MKL	Benign	0.043	N
LIST_S2	Benign	0.67	T;T
M_CAP	Benign	0.0084	T
MetaRNN	Benign	0.12	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.69	N;N
MutationTaster	Benign	0.74	D;D;D
PrimateAI	Uncertain	0.78	T
PROVEAN	Benign	-0.67	N;N
REVEL	Benign	0.023
Sift	Benign	0.13	T;T
Sift4G	Benign	0.22	T;T
Polyphen		0.0030	B;.
Vest4		0.099
MutPred		0.32		Gain of phosphorylation at G4 (P = 0.0233);Gain of phosphorylation at G4 (P = 0.0233);
MVP		0.12
MPC		0.38
ClinPred		0.36	T
GERP RS		3.8
Varity_R		0.15
gMVP		0.46

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

Publications

LitVar

Other links and lift over

dbSNP: rs797046116; hg19: chrX-74742850;