X-75421973-C-T

Position:

• chrX-75421973-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_144969.3(ZDHHC15):​c.754G>A​(p.Val252Met) variant causes a missense change. The variant allele was found at a frequency of 0.000000913 in 1,095,644 control chromosomes in the GnomAD database, with no homozygous occurrence. There are no hemizygote samples in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 22)
  • Exomes 𝑓: 9.1e-7 (0 hom. 0 hem.)
• Consequence: ZDHHC15 NM_144969.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.79

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 Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.20120692).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZDHHC15	NM_144969.3	c.754G>A	p.Val252Met	missense_variant	9/12	ENST00000373367.8	NP_659406.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZDHHC15	ENST00000373367.8	c.754G>A	p.Val252Met	missense_variant	9/12	1	NM_144969.3	ENSP00000362465	P1
ZDHHC15	ENST00000541184.1	c.727G>A	p.Val243Met	missense_variant	8/11	2		ENSP00000445420

Frequencies

GnomAD3 genomes Cov.: 22

GnomAD4 exome AF: 9.13e-7 AC: 1 AN: 1095644 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 361470

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: 0.00000119

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 provided Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Greenwood Genetic Center Diagnostic Laboratories, Greenwood Genetic Center

Jun 21, 2024

Gene of Uncertain Significance -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.20
BayesDel_addAF	Benign	-0.11	T
BayesDel_noAF	Benign	-0.39
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Benign	0.16	T;.
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Uncertain	0.92	D;D
M_CAP	Benign	0.027	D
MetaRNN	Benign	0.20	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.4	L;.
MutationTaster	Benign	1.0	D;D;D
PrimateAI	Uncertain	0.69	T
PROVEAN	Benign	-1.5	N;N
REVEL	Benign	0.10
Sift	Benign	0.33	T;T
Sift4G	Benign	0.35	T;T
Polyphen		0.64	P;.
Vest4		0.21
MutPred		0.34		Gain of disorder (P = 0.0813);.;
MVP		0.24
MPC		0.39
ClinPred		0.73	D
GERP RS		5.4
Varity_R		0.51
gMVP		0.77

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chrX-74641808;