6-157672910-G-A

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_Strong BP6_Very_Strong BS2

The NM_024630.3(ZDHHC14):c.1255G>A(p.Ala419Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00765 in 1,604,682 control chromosomes in the GnomAD database, including 83 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0097 (12 hom., cov: 31)
  • Exomes 𝑓: 0.0074 (71 hom.)
• Consequence: ZDHHC14 NM_024630.3 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.108

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 Benign. Variant got -16 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0029196143).
• BP6: Variant 6-157672910-G-A is Benign according to our data. Variant chr6-157672910-G-A is described in ClinVar as [Benign]. Clinvar id is 788356.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS2: High Homozygotes in GnomAd at 12 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ZDHHC14	NM_024630.3	c.1255G>A	p.Ala419Thr	missense_variant	9/9	ENST00000359775.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ZDHHC14	ENST00000359775.10	c.1255G>A	p.Ala419Thr	missense_variant	9/9	1	NM_024630.3	A1

Frequencies

GnomAD3 genomes AF: 0.00974 AC: 1481 AN: 152110 Hom.: 12 Cov.: 31

Gnomad AFR AF: 0.00978

Gnomad AMI AF: 0.00110

Gnomad AMR AF: 0.00569

Gnomad ASJ AF: 0.00115

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.0350

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.00872

Gnomad OTH AF: 0.00814

GnomAD3 exomes AF: 0.00731 AC: 1646 AN: 225294 Hom.: 15 AF XY: 0.00703 AC XY: 870 AN XY: 123728

Gnomad AFR exome AF: 0.00938

Gnomad AMR exome AF: 0.00309

Gnomad ASJ exome AF: 0.000952

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00130

Gnomad FIN exome AF: 0.0312

Gnomad NFE exome AF: 0.00757

Gnomad OTH exome AF: 0.0107

GnomAD4 exome AF: 0.00743 AC: 10788 AN: 1452452 Hom.: 71 Cov.: 33 AF XY: 0.00731 AC XY: 5284 AN XY: 722408

Gnomad4 AFR exome AF: 0.00964

Gnomad4 AMR exome AF: 0.00331

Gnomad4 ASJ exome AF: 0.000926

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00165

Gnomad4 FIN exome AF: 0.0304

Gnomad4 NFE exome AF: 0.00743

Gnomad4 OTH exome AF: 0.00653

GnomAD4 genome AF: 0.00974 AC: 1483 AN: 152230 Hom.: 12 Cov.: 31 AF XY: 0.0109 AC XY: 809 AN XY: 74426

Gnomad4 AFR AF: 0.00980

Gnomad4 AMR AF: 0.00568

Gnomad4 ASJ AF: 0.00115

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000208

Gnomad4 FIN AF: 0.0350

Gnomad4 NFE AF: 0.00872

Gnomad4 OTH AF: 0.00806

Alfa AF: 0.00648 Hom.: 3

Bravo AF: 0.00744

TwinsUK AF: 0.00512 AC: 19

ALSPAC AF: 0.00701 AC: 27

ESP6500AA AF: 0.00803 AC: 35

ESP6500EA AF: 0.00680 AC: 58

ExAC AF: 0.00696 AC: 834

Asia WGS AF: 0.00260 AC: 10 AN: 3476

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	Invitae	Jan 02, 2019	- -
Benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Sep 01, 2022	ZDHHC14: BP4, BS1, BS2 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.067
BayesDel_addAF	Benign	-0.72	T
BayesDel_noAF	Benign	-0.80
Cadd	Benign	3.0
Dann	Benign	0.91
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.074	N
LIST_S2	Benign	0.63	T;T
MetaRNN	Benign	0.0029	T;T
MetaSVM	Benign	-0.80	T
MutationTaster	Benign	1.0	N;N
PrimateAI	Benign	0.34	T
PROVEAN	Benign	0.080	N;N
REVEL	Benign	0.10
Sift	Benign	0.53	T;T
Sift4G	Benign	0.42	T;T
Polyphen		0.0	B;B
Vest4		0.021
MVP		0.082
MPC		0.32
ClinPred		0.0040	T
GERP RS		-11
Varity_R		0.023
gMVP		0.14

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: rs73571886; hg19: chr6-158093942;