Genetic Variant NM_144969.3:c.*3696G>A (chrX-75369282-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_144969.3(ZDHHC15):c.*3696G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.63 ( 17700 hom., 19756 hem., cov: 22)

Exomes 𝑓: 0.57 ( 1 hom. 2 hem. )

Failed GnomAD Quality Control

Consequence

ZDHHC15
NM_144969.3 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.463

Publications

4 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 -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.92).

BA1

GnomAdExome4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.118 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZDHHC15	NM_144969.3 link	c.*3696G>A		3_prime_UTR_variant	Exon 12 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.*3696G>A		3_prime_UTR_variant	Exon 12 of 12	1	NM_144969.3	ENSP00000362465.3		Q96MV8-1
ZDHHC15	ENST00000541184.1 link	c.*3696G>A		3_prime_UTR_variant	Exon 11 of 11	2		ENSP00000445420.1		Q96MV8-3

Frequencies

GnomAD3 genomes

AF:

0.633

AC:

68381

AN:

107989

Hom.:

17714

Cov.:

show subpopulations

Gnomad AFR

AF:

0.297

Gnomad AMI

AF:

0.971

Gnomad AMR

AF:

0.642

Gnomad ASJ

AF:

0.855

Gnomad EAS

AF:

0.128

Gnomad SAS

AF:

0.508

Gnomad FIN

AF:

0.822

Gnomad MID

AF:

0.835

Gnomad NFE

AF:

0.822

Gnomad OTH

AF:

0.688

GnomAD4 exome

AF:

0.571

AC:

AN:

Hom.:

Cov.:

AF XY:

0.667

AC XY:

AN XY:

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.667

AC:

AN:

Other (OTH)

AF:

1.00

AC:

AN:

GnomAD4 genome

Data not reliable, filtered out with message: InbreedingCoeff

AF:

0.633

AC:

68370

AN:

108040

Hom.:

17700

Cov.:

AF XY:

0.649

AC XY:

19756

AN XY:

30442

show subpopulations

African (AFR)

AF:

0.297

AC:

8783

AN:

29611

American (AMR)

AF:

0.642

AC:

6414

AN:

9990

Ashkenazi Jewish (ASJ)

AF:

0.855

AC:

2233

AN:

2612

East Asian (EAS)

AF:

0.128

AC:

420

AN:

3294

South Asian (SAS)

AF:

0.508

AC:

1215

AN:

2392

European-Finnish (FIN)

AF:

0.822

AC:

4469

AN:

5437

Middle Eastern (MID)

AF:

0.824

AC:

173

AN:

210

European-Non Finnish (NFE)

AF:

0.822

AC:

43003

AN:

52344

Other (OTH)

AF:

0.680

AC:

999

AN:

1469

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

Heterozygous variant carriers

684

1368

2051

2735

3419

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

580

1160

1740

2320

2900

<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:

0.746

Hom.:

24036

Bravo

AF:

0.595

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.92

CADD

Benign

0.15

(source)

DANN

Benign

0.25

PhyloP100

-0.46

Mutation Taster

=100/0

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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