X-75421980-G-A

Variant summary

Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP4_StrongBP6_Very_StrongBP7BS2

The NM_144969.3(ZDHHC15):​c.747C>T​(p.Cys249=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000874 in 1,206,364 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 343 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.00044 ( 0 hom., 10 hem., cov: 22)
Exomes 𝑓: 0.00092 ( 0 hom. 333 hem. )

Consequence

ZDHHC15
NM_144969.3 synonymous

Scores

2

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.106
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]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -17 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.52).
BP6
Variant X-75421980-G-A is Benign according to our data. Variant chrX-75421980-G-A is described in ClinVar as [Benign]. Clinvar id is 199186.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
Synonymous conserved (PhyloP=0.106 with no splicing effect.
BS2
High Hemizygotes in GnomAd4 at 10 XL gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
ZDHHC15NM_144969.3 linkuse as main transcriptc.747C>T p.Cys249= synonymous_variant 9/12 ENST00000373367.8 NP_659406.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
ZDHHC15ENST00000373367.8 linkuse as main transcriptc.747C>T p.Cys249= synonymous_variant 9/121 NM_144969.3 ENSP00000362465 P1Q96MV8-1
ZDHHC15ENST00000541184.1 linkuse as main transcriptc.720C>T p.Cys240= synonymous_variant 8/112 ENSP00000445420 Q96MV8-3

Frequencies

GnomAD3 genomes
AF:
0.000439
AC:
49
AN:
111733
Hom.:
0
Cov.:
22
AF XY:
0.000295
AC XY:
10
AN XY:
33915
show subpopulations
Gnomad AFR
AF:
0.000293
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.000752
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.000537
AC:
96
AN:
178820
Hom.:
0
AF XY:
0.000581
AC XY:
37
AN XY:
63654
show subpopulations
Gnomad AFR exome
AF:
0.000312
Gnomad AMR exome
AF:
0.000113
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.000879
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.000885
Gnomad OTH exome
AF:
0.000459
GnomAD4 exome
AF:
0.000918
AC:
1005
AN:
1094631
Hom.:
0
Cov.:
30
AF XY:
0.000924
AC XY:
333
AN XY:
360539
show subpopulations
Gnomad4 AFR exome
AF:
0.0000763
Gnomad4 AMR exome
AF:
0.0000862
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.000749
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00108
Gnomad4 OTH exome
AF:
0.00107
GnomAD4 genome
AF:
0.000439
AC:
49
AN:
111733
Hom.:
0
Cov.:
22
AF XY:
0.000295
AC XY:
10
AN XY:
33915
show subpopulations
Gnomad4 AFR
AF:
0.000293
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000752
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.000391
Hom.:
2
Bravo
AF:
0.000521

ClinVar

Significance: Benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

not specified Benign:2
Benign, criteria provided, single submitterclinical testingGenetic Services Laboratory, University of ChicagoAug 05, 2019- -
Benign, criteria provided, single submitterclinical testingEurofins Ntd Llc (ga)Jan 06, 2015- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.52
CADD
Benign
8.1
DANN
Benign
0.64

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.010
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.

Other links and lift over

dbSNP: rs147278537; hg19: chrX-74641815; API