X-75431511-A-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

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
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 6.89

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 -14 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_single_submitter, 1 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 GnomAd at 2 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ZDHHC15	NM_144969.3	c.389T>A	p.Phe130Tyr	missense_variant	5/12	ENST00000373367.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ZDHHC15	ENST00000373367.8	c.389T>A	p.Phe130Tyr	missense_variant	5/12	1	NM_144969.3	P1
ZDHHC15	ENST00000541184.1	c.362T>A	p.Phe121Tyr	missense_variant	4/11	2

Frequencies

GnomAD3 genomes AF: 0.00186 AC: 204 AN: 109888 Hom.: 2 Cov.: 22 AF XY: 0.00199 AC XY: 64 AN XY: 32140

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.: 8 AF XY: 0.00335 AC XY: 216 AN XY: 64417

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.: 9 Cov.: 29 AF XY: 0.000991 AC XY: 358 AN XY: 361411

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.: 3 Cov.: 22 AF XY: 0.00199 AC XY: 64 AN XY: 32202

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.: 22

Bravo AF: 0.00295

ESP6500AA AF: 0.000261 AC: 1

ESP6500EA AF: 0.000595 AC: 4

ExAC AF: 0.00367 AC: 445

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

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	T
BayesDel_noAF	Benign	-0.35
Cadd	Benign	19
Dann	Benign	0.96
DEOGEN2	Benign	0.082	T;.
FATHMM_MKL	Pathogenic	1.0	D
LIST_S2	Benign	0.76	T;T
MetaRNN	Benign	0.013	T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	-0.56	N;.
MutationTaster	Benign	1.0	D;D;D
PrimateAI	Pathogenic	0.84	D
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	T
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

Other links and lift over

dbSNP: rs144514141; hg19: chrX-74651346;