X-75417103-G-A

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_Strong BP7 BS2

The NM_144969.3(ZDHHC15):c.951C>T(p.Asn317=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000299 in 1,205,645 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 12 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00011 (0 hom., 3 hem., cov: 23)
  • Exomes 𝑓: 0.000022 (0 hom. 9 hem.)
• Consequence: ZDHHC15 NM_144969.3 synonymous
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.445

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]

ACMG classification

Verdict is Benign. Variant got -9 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.76).
• BP7: Synonymous conserved (PhyloP=-0.445 with no splicing effect.
• BS2: High Hemizygotes in GnomAd at 3 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ZDHHC15	NM_144969.3	c.951C>T	p.Asn317=	synonymous_variant	10/12	ENST00000373367.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ZDHHC15	ENST00000373367.8	c.951C>T	p.Asn317=	synonymous_variant	10/12	1	NM_144969.3	P1
ZDHHC15	ENST00000541184.1	c.924C>T	p.Asn308=	synonymous_variant	9/11	2

Frequencies

GnomAD3 genomes AF: 0.000108 AC: 12 AN: 111577 Hom.: 0 Cov.: 23 AF XY: 0.0000889 AC XY: 3 AN XY: 33749

Gnomad AFR AF: 0.0000652

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000572

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: 0.0000188

Gnomad OTH AF: 0.00200

GnomAD3 exomes AF: 0.0000656 AC: 12 AN: 182908 Hom.: 0 AF XY: 0.0000594 AC XY: 4 AN XY: 67380

Gnomad AFR exome AF: 0.000152

Gnomad AMR exome AF: 0.000183

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: 0.0000122

Gnomad OTH exome AF: 0.000885

GnomAD4 exome AF: 0.0000219 AC: 24 AN: 1094017 Hom.: 0 Cov.: 28 AF XY: 0.0000250 AC XY: 9 AN XY: 359739

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.000314

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: 0.0000107

Gnomad4 OTH exome AF: 0.0000871

GnomAD4 genome AF: 0.000107 AC: 12 AN: 111628 Hom.: 0 Cov.: 23 AF XY: 0.0000887 AC XY: 3 AN XY: 33810

Gnomad4 AFR AF: 0.0000650

Gnomad4 AMR AF: 0.000572

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000188

Gnomad4 OTH AF: 0.00198

Alfa AF: 0.000130 Hom.: 1

Bravo AF: 0.000147

EpiCase AF: 0.00

EpiControl AF: 0.0000593

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Eurofins Ntd Llc (ga)

Jun 23, 2015

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.76
Cadd	Benign	0.68
Dann	Benign	0.53

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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

Other links and lift over

dbSNP: rs192529997; hg19: chrX-74636938;