rs797046116

Variant names:

• chrX-75523015-C-T
• rs797046116
• NM_144969.3:c.10G>A

Variant summary

Our verdict is Likely benign. The variant received -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. 13/21 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
• 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

ENSG00000302260 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -6 ACMG points.

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

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.10G>A	p.Gly4Ser	missense	Exon 1 of 12	NP_659406.1	Q96MV8-1
	ZDHHC15	NM_001146256.2		c.10G>A	p.Gly4Ser	missense	Exon 1 of 11	NP_001139728.1	Q96MV8-3
	ZDHHC15	NM_001146257.2		c.10G>A	p.Gly4Ser	missense	Exon 1 of 3	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.10G>A	p.Gly4Ser	missense	Exon 1 of 12	ENSP00000362465.3	Q96MV8-1
	ZDHHC15	ENST00000858993.1		c.10G>A	p.Gly4Ser	missense	Exon 1 of 11	ENSP00000529052.1
	ZDHHC15	ENST00000858994.1		c.10G>A	p.Gly4Ser	missense	Exon 1 of 12	ENSP00000529053.1

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

African (AFR) AF: 0.00 AC: 0 AN: 26347

American (AMR) AF: 0.00 AC: 0 AN: 34785

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19266

East Asian (EAS) AF: 0.00 AC: 0 AN: 30116

South Asian (SAS) AF: 0.00 AC: 0 AN: 53488

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40318

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4118

European-Non Finnish (NFE) AF: 0.00000476 AC: 4 AN: 840376

Other (OTH) AF: 0.00 AC: 0 AN: 45976

GnomAD4 genome Cov.: 22

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

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
M_CAP	Benign	0.0084	T
MetaRNN	Benign	0.12	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.69	N
PhyloP100		1.4
PrimateAI	Uncertain	0.78	T
PROVEAN	Benign	-0.67	N
REVEL	Benign	0.023
Sift	Benign	0.13	T
Sift4G	Benign	0.22	T
Polyphen		0.0030	B
Vest4		0.099
MutPred		0.32		Gain of phosphorylation at G4 (P = 0.0233)
MVP		0.12
MPC		0.38
ClinPred		0.36	T
GERP RS		3.8
PromoterAI		-0.071	Neutral
Varity_R		0.15
gMVP		0.46
Mutation Taster		=94/6	polymorphism

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: rs797046116; hg19: chrX-74742850;