rs144514141

Variant names:

Variant summary

Our verdict is Benign. The variant received -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. 12/20 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

Publications

1 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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 VariationId 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. GnomAdExome4 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 GnomAdExome4. There are 358 alleles in the male GnomAdExome4 subpopulation. Median coverage is 29. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 3 XL,Unknown gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZDHHC15	NM_144969.3 link	c.389T>A	p.Phe130Tyr	missense_variant	Exon 5 of 12	ENST00000373367.8	NP_659406.1	Q96MV8-1B3KY34

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZDHHC15	ENST00000373367.8 link	c.389T>A	p.Phe130Tyr	missense_variant	Exon 5 of 12	1	NM_144969.3	ENSP00000362465.3		Q96MV8-1
ZDHHC15	ENST00000541184.1 link	c.362T>A	p.Phe121Tyr	missense_variant	Exon 4 of 11	2		ENSP00000445420.1		Q96MV8-3

Frequencies

GnomAD3 genomes

AF:

0.00186

AC:

204

AN:

109888

Hom.:

Cov.:

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

GnomAD2 exomes

AF:

0.00485

AC:

870

AN:

179405

AF XY:

0.00335

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 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

African (AFR)

AF:

0.000493

AC:

AN:

26356

American (AMR)

AF:

0.0274

AC:

961

AN:

35014

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

19316

East Asian (EAS)

AF:

0.0000994

AC:

AN:

30176

South Asian (SAS)

AF:

0.00

AC:

AN:

53526

European-Finnish (FIN)

AF:

0.000817

AC:

AN:

40398

Middle Eastern (MID)

AF:

0.000242

AC:

AN:

4124

European-Non Finnish (NFE)

AF:

0.000307

AC:

258

AN:

841025

Other (OTH)

AF:

0.000718

AC:

AN:

45976

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.467

Heterozygous variant carriers

126

168

210

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

110

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00189

AC:

208

AN:

109940

Hom.:

Cov.:

AF XY:

0.00199

AC XY:

AN XY:

32202

show subpopulations

African (AFR)

AF:

0.000297

AC:

AN:

30297

American (AMR)

AF:

0.0160

AC:

163

AN:

10171

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2634

East Asian (EAS)

AF:

0.00

AC:

AN:

3466

South Asian (SAS)

AF:

0.00

AC:

AN:

2461

European-Finnish (FIN)

AF:

0.000523

AC:

AN:

5737

Middle Eastern (MID)

AF:

0.00

AC:

AN:

214

European-Non Finnish (NFE)

AF:

0.000587

AC:

AN:

52795

Other (OTH)

AF:

0.00135

AC:

AN:

1486

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.510

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

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

Jun 12, 2017

Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

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

(source)

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;.

PhyloP100

6.9

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

Mutation Taster

=72/28

polymorphism (auto)

(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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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over