rs1470113586

Variant names:

• chrX-75424763-A-C
• rs1470113586
• NM_144969.3:c.625T>G

Your query was ambiguous. Multiple possible variants found:

• chrX-75424763-A-C
• chrX-75424763-A-G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_144969.3(ZDHHC15):​c.625T>G​(p.Ser209Ala) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. S209P) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 22)
• Consequence: ZDHHC15 NM_144969.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.17
• 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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.092018396).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZDHHC15	NM_144969.3	c.625T>G	p.Ser209Ala	missense_variant	Exon 8 of 12	ENST00000373367.8	NP_659406.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZDHHC15	ENST00000373367.8	c.625T>G	p.Ser209Ala	missense_variant	Exon 8 of 12	1	NM_144969.3	ENSP00000362465.3
ZDHHC15	ENST00000541184.1	c.598T>G	p.Ser200Ala	missense_variant	Exon 7 of 11	2		ENSP00000445420.1

Frequencies

GnomAD3 genomes Cov.: 22

GnomAD4 exome Cov.: 29

GnomAD4 genome Cov.: 22

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.096
BayesDel_addAF	Benign	-0.40	T
BayesDel_noAF	Benign	-0.81
CADD	Benign	19
DANN	Benign	0.41
DEOGEN2	Benign	0.052	T;.
FATHMM_MKL	Uncertain	0.82	D
LIST_S2	Benign	0.78	T;T
M_CAP	Benign	0.034	D
MetaRNN	Benign	0.092	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-0.77	N;.
PhyloP100		5.2
PrimateAI	Uncertain	0.63	T
PROVEAN	Benign	1.3	N;N
REVEL	Benign	0.058
Sift	Benign	1.0	T;T
Sift4G	Benign	1.0	T;T
Polyphen		0.015	B;.
Vest4		0.19
MutPred		0.45		Loss of stability (P = 0.0371);.;
MVP		0.12
MPC		0.32
ClinPred		0.52	D
GERP RS		5.6
Varity_R		0.29
gMVP		0.34
Mutation Taster		=84/16	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: rs1470113586; hg19: chrX-74644598;