6-157672814-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_024630.3(ZDHHC14):c.1159G>A(p.Asp387Asn) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000822 in 1,460,278 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.0000082 (0 hom.)
• Consequence: ZDHHC14 NM_024630.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 9.38

Genes affected

ZDHHC14 (HGNC:20341): (zinc finger DHHC-type palmitoyltransferase 14) Enables palmitoyltransferase activity. Involved in peptidyl-L-cysteine S-palmitoylation. Located in endoplasmic reticulum. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.079292536).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ZDHHC14	NM_024630.3	c.1159G>A	p.Asp387Asn	missense_variant	9/9	ENST00000359775.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ZDHHC14	ENST00000359775.10	c.1159G>A	p.Asp387Asn	missense_variant	9/9	1	NM_024630.3	A1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD3 exomes AF: 0.0000165 AC: 4 AN: 242986 Hom.: 0 AF XY: 0.0000225 AC XY: 3 AN XY: 133042

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000221

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000822 AC: 12 AN: 1460278 Hom.: 0 Cov.: 33 AF XY: 0.0000110 AC XY: 8 AN XY: 726498

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000252

Gnomad4 SAS exome AF: 0.0000232

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000720

Gnomad4 OTH exome AF: 0.0000166

GnomAD4 genome Cov.: 31

ExAC AF: 0.0000165 AC: 2

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jul 20, 2021

The c.1159G>A (p.D387N) alteration is located in exon 9 (coding exon 9) of the ZDHHC14 gene. This alteration results from a G to A substitution at nucleotide position 1159, causing the aspartic acid (D) at amino acid position 387 to be replaced by an asparagine (N). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.079
BayesDel_addAF	Benign	-0.45	T
BayesDel_noAF	Benign	-0.60
Cadd	Uncertain	23
Dann	Uncertain	1.0
Eigen	Benign	0.036
Eigen_PC	Uncertain	0.24
FATHMM_MKL	Pathogenic	1.0	D
LIST_S2	Benign	0.84	T;D
M_CAP	Benign	0.015	T
MetaRNN	Benign	0.079	T;T
MetaSVM	Benign	-1.0	T
MutationTaster	Benign	0.78	D;D
PrimateAI	Uncertain	0.57	T
PROVEAN	Benign	0.48	N;N
REVEL	Benign	0.15
Sift	Benign	0.15	T;T
Sift4G	Benign	0.41	T;T
Polyphen		0.0050	B;B
Vest4		0.10
MutPred		0.16		.;Loss of phosphorylation at T385 (P = 0.1036);
MVP		0.32
MPC		0.33
ClinPred		0.31	T
GERP RS		5.6
Varity_R		0.079
gMVP		0.27

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: rs754474697; hg19: chr6-158093846;