Genetic Variant NM_144969.3:c.32G>A (chrX-75522993-C-T) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_144969.3(ZDHHC15):c.32G>A(p.Gly11Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000911 in 1,097,311 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 1 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. 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. G11A) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 22)

Exomes 𝑓: 9.1e-7 ( 0 hom. 1 hem. )

Consequence

ZDHHC15
NM_144969.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.892

Publications

0 publications found

Variant links:

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

ZDHHC15 links:

ENSG00000302260 (HGNC:):

ENSG00000302260 links:

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ACMG classification

Classification was made for transcript

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=0.105311155).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZDHHC15	NM_144969.3 link	c.32G>A	p.Gly11Glu	missense_variant	Exon 1 of 12	ENST00000373367.8	NP_659406.1	Q96MV8-1B3KY34

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
ZDHHC15	ENST00000373367.8 link	c.32G>A	p.Gly11Glu	missense_variant	Exon 1 of 12	1	NM_144969.3	ENSP00000362465.3	Q96MV8-1
ZDHHC15	ENST00000541184.1 link	c.32G>A	p.Gly11Glu	missense_variant	Exon 1 of 11	2		ENSP00000445420.1	Q96MV8-3
ZDHHC15	ENST00000482827.1 link	n.18G>A		non_coding_transcript_exon_variant	Exon 1 of 2	5
ENSG00000302260	ENST00000785233.1 link	n.-244C>T		upstream_gene_variant

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

9.11e-7

AC:

AN:

1097311

Hom.:

Cov.:

AF XY:

0.00000276

AC XY:

AN XY:

362703

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

26387

American (AMR)

AF:

0.00

AC:

AN:

35106

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

19338

East Asian (EAS)

AF:

0.00

AC:

AN:

30185

South Asian (SAS)

AF:

0.00

AC:

AN:

53930

European-Finnish (FIN)

AF:

0.00

AC:

AN:

40469

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4135

European-Non Finnish (NFE)

AF:

0.00000119

AC:

AN:

841698

Other (OTH)

AF:

0.00

AC:

AN:

46063

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.17

BayesDel_addAF

Benign

-0.23

BayesDel_noAF

Benign

-0.57

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.093

T;.

FATHMM_MKL

Benign

0.25

LIST_S2

Uncertain

0.87

D;D

M_CAP

Benign

0.0093

MetaRNN

Benign

0.11

T;T

MetaSVM

Benign

-0.97

MutationAssessor

Benign

1.3

L;L

PhyloP100

0.89

PrimateAI

Pathogenic

0.80

PROVEAN

Benign

-0.23

N;N

REVEL

Benign

0.070

Sift

Benign

0.24

T;T

Sift4G

Benign

0.24

T;T

Polyphen

0.32

B;.

Vest4

0.13

MutPred

0.46

Gain of methylation at K6 (P = 0.0634);Gain of methylation at K6 (P = 0.0634);

MVP

0.13

MPC

0.64

ClinPred

0.43

GERP RS

2.8

PromoterAI

0.13

Neutral

(source)

Varity_R

0.16

gMVP

0.60

Mutation Taster

=92/8

polymorphism

(source)

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

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NM_144969.3:c.32G>A

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over