Variant X-75424755-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3

The NM_144969.3(ZDHHC15):c.633C>A(p.Phe211Leu) variant causes a missense change. The variant allele was found at a frequency of 0.00000275 in 1,089,730 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 1 hemizygotes in GnomAD. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 22)

Exomes 𝑓: 0.0000028 ( 0 hom. 1 hem. )

Consequence

ZDHHC15
NM_144969.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.57

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 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.782

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ZDHHC15	NM_144969.3 linkuse as main transcript	c.633C>A	p.Phe211Leu	missense_variant	8/12	ENST00000373367.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ZDHHC15	ENST00000373367.8 linkuse as main transcript	c.633C>A	p.Phe211Leu	missense_variant	8/12	1	NM_144969.3	P1	Q96MV8-1
ZDHHC15	ENST00000541184.1 linkuse as main transcript	c.606C>A	p.Phe202Leu	missense_variant	7/11	2			Q96MV8-3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000118

AC:

AN:

169630

Hom.:

AF XY:

0.0000180

AC XY:

AN XY:

55536

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000265

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000275

AC:

AN:

1089730

Hom.:

Cov.:

AF XY:

0.00000281

AC XY:

AN XY:

356254

show subpopulations

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:

0.00000358

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ExAC

AF:

0.0000165

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Nov 03, 2022

The c.633C>A (p.F211L) alteration is located in exon 8 (coding exon 8) of the ZDHHC15 gene. This alteration results from a C to A substitution at nucleotide position 633, causing the phenylalanine (F) at amino acid position 211 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.98

BayesDel_addAF

Uncertain

0.065

BayesDel_noAF

Benign

-0.14

Cadd

Pathogenic

Dann

Uncertain

0.98

DEOGEN2

Benign

0.40

T;.

FATHMM_MKL

Pathogenic

0.97

LIST_S2

Uncertain

0.86

D;D

M_CAP

Pathogenic

0.34

MetaRNN

Pathogenic

0.78

D;D

MetaSVM

Benign

-0.99

MutationAssessor

Benign

1.3

L;.

MutationTaster

Benign

1.0

D;D;N

PrimateAI

Pathogenic

0.87

PROVEAN

Pathogenic

-5.8

D;D

REVEL

Benign

0.25

Sift

Uncertain

0.026

D;D

Sift4G

Benign

0.087

T;T

Polyphen

1.0

D;.

Vest4

0.85

MutPred

0.40

Loss of methylation at K210 (P = 0.0306);.;

MVP

0.69

MPC

0.63

ClinPred

0.85

GERP RS

4.7

Varity_R

0.74

gMVP

0.84

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.17

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over