Variant X-75431511-A-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_144969.3(ZDHHC15):c.389T>A(p.Phe130Tyr) variant causes a missense change. The variant allele was found at a frequency of 0.00125 in 1,205,851 control chromosomes in the GnomAD database, including 12 homozygotes. There are 422 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 11/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0019 ( 3 hom., 64 hem., cov: 22)

Exomes 𝑓: 0.0012 ( 9 hom. 358 hem. )

Consequence

ZDHHC15
NM_144969.3 missense

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 6.89

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:

ZDHHC15 (HGNC:):

ZDHHC15 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.013141543).

BP6

Variant X-75431511-A-T is Benign according to our data. Variant chrX-75431511-A-T is described in ClinVar as [Likely_benign]. Clinvar id is 445942.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population amr. gnomad4_exome allele frequency = 0.00119 (1302/1095911) while in subpopulation AMR AF= 0.0274 (961/35014). AF 95% confidence interval is 0.026. There are 9 homozygotes in gnomad4_exome. There are 358 alleles in male gnomad4_exome subpopulation. Median coverage is 29. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 3 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZDHHC15	NM_144969.3 linkuse as main transcript	c.389T>A	p.Phe130Tyr	missense_variant	5/12	ENST00000373367.8	NP_659406.1	Q96MV8-1B3KY34

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZDHHC15	ENST00000373367.8 linkuse as main transcript	c.389T>A	p.Phe130Tyr	missense_variant	5/12	1	NM_144969.3	ENSP00000362465.3		Q96MV8-1
ZDHHC15	ENST00000541184.1 linkuse as main transcript	c.362T>A	p.Phe121Tyr	missense_variant	4/11	2		ENSP00000445420.1		Q96MV8-3

Frequencies

GnomAD3 genomes

AF:

0.00186

AC:

204

AN:

109888

Hom.:

Cov.:

AF XY:

0.00199

AC XY:

AN XY:

32140

show subpopulations

Gnomad AFR

AF:

0.000298

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0157

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000523

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000587

Gnomad OTH

AF:

0.00136

GnomAD3 exomes

AF:

0.00485

AC:

870

AN:

179405

Hom.:

AF XY:

0.00335

AC XY:

216

AN XY:

64417

show subpopulations

Gnomad AFR exome

AF:

0.000543

Gnomad AMR exome

AF:

0.0283

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000733

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000817

Gnomad NFE exome

AF:

0.000674

Gnomad OTH exome

AF:

0.00798

GnomAD4 exome

AF:

0.00119

AC:

1302

AN:

1095911

Hom.:

Cov.:

AF XY:

0.000991

AC XY:

358

AN XY:

361411

show subpopulations

Gnomad4 AFR exome

AF:

0.000493

Gnomad4 AMR exome

AF:

0.0274

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000994

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.000817

Gnomad4 NFE exome

AF:

0.000307

Gnomad4 OTH exome

AF:

0.000718

GnomAD4 genome

AF:

0.00189

AC:

208

AN:

109940

Hom.:

Cov.:

AF XY:

0.00199

AC XY:

AN XY:

32202

show subpopulations

Gnomad4 AFR

AF:

0.000297

Gnomad4 AMR

AF:

0.0160

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.000523

Gnomad4 NFE

AF:

0.000587

Gnomad4 OTH

AF:

0.00135

Alfa

AF:

0.000829

Hom.:

Bravo

AF:

0.00295

ESP6500AA

AF:

0.000261

AC:

ESP6500EA

AF:

0.000595

AC:

ExAC

AF:

0.00367

AC:

445

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Likely benign, criteria provided, single submitter	clinical testing	Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics	Jun 12, 2017	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.20

BayesDel_addAF

Benign

-0.41

BayesDel_noAF

Benign

-0.35

CADD

Benign

DANN

Benign

0.96

DEOGEN2

Benign

0.082

T;.

FATHMM_MKL

Pathogenic

1.0

LIST_S2

Benign

0.76

T;T

MetaRNN

Benign

0.013

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

-0.56

N;.

PrimateAI

Pathogenic

0.84

PROVEAN

Benign

1.6

N;N

REVEL

Benign

0.25

Sift

Benign

1.0

T;T

Sift4G

Benign

1.0

T;T

Polyphen

0.030

B;.

Vest4

0.52

MVP

0.34

MPC

0.46

ClinPred

0.013

GERP RS

5.1

Varity_R

0.39

gMVP

0.74

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

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