Genetic Variant NM_024630.3:c.213C>G (chr6-157382234-C-G) – ACMG Classification: Uncertain_significance (3 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3

The NM_024630.3(ZDHHC14):c.213C>G(p.Ile71Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,459,794 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 31)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

ZDHHC14
NM_024630.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.22

Variant links:

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]

ZDHHC14 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.821

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZDHHC14	NM_024630.3 link	c.213C>G	p.Ile71Met	missense_variant	Exon 1 of 9	ENST00000359775.10	NP_078906.2	Q8IZN3-1
ZDHHC14	NM_153746.2 link	c.213C>G	p.Ile71Met	missense_variant	Exon 1 of 9		NP_714968.1	Q8IZN3-2
ZDHHC14	XM_047419366.1 link	c.213C>G	p.Ile71Met	missense_variant	Exon 1 of 9		XP_047275322.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZDHHC14	ENST00000359775.10 link	c.213C>G	p.Ile71Met	missense_variant	Exon 1 of 9	1	NM_024630.3	ENSP00000352821.5		Q8IZN3-1
ZDHHC14	ENST00000414563.6 link	c.213C>G	p.Ile71Met	missense_variant	Exon 1 of 9	1		ENSP00000410713.2		Q8IZN3-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000402

AC:

AN:

248480

Hom.:

AF XY:

0.00000743

AC XY:

AN XY:

134528

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

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:

0.00000888

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000137

AC:

AN:

1459794

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

726180

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

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:

0.00000180

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Feb 07, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.213C>G (p.I71M) alteration is located in exon 1 (coding exon 1) of the ZDHHC14 gene. This alteration results from a C to G substitution at nucleotide position 213, causing the isoleucine (I) at amino acid position 71 to be replaced by a methionine (M). 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

Pathogenic

0.63

BayesDel_addAF

Pathogenic

0.22

BayesDel_noAF

Uncertain

0.070

CADD

Uncertain

DANN

Uncertain

0.99

DEOGEN2

Benign

0.15

.;T

Eigen

Uncertain

0.43

Eigen_PC

Uncertain

0.35

FATHMM_MKL

Uncertain

0.87

LIST_S2

Uncertain

0.92

D;D

M_CAP

Benign

0.044

MetaRNN

Pathogenic

0.82

D;D

MetaSVM

Benign

-0.58

MutationAssessor

Uncertain

2.4

M;M

PrimateAI

Uncertain

0.77

PROVEAN

Uncertain

-2.7

D;D

REVEL

Uncertain

0.38

Sift

Benign

0.071

T;T

Sift4G

Benign

0.075

T;T

Polyphen

0.96

D;D

Vest4

0.83

MutPred

0.52

Loss of stability (P = 0.0308);Loss of stability (P = 0.0308);

MVP

0.81

MPC

1.8

ClinPred

0.88

GERP RS

2.7

Varity_R

0.46

gMVP

0.94

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over