Variant 9-14662218-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate

The NM_178566.6(ZDHHC21):c.362C>A(p.Pro121Gln) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000138 in 1,596,098 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: 𝑓 0.000079 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0000069 ( 0 hom. )

Consequence

ZDHHC21
NM_178566.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 9.18

Variant links:

Genes affected

ZDHHC21 (HGNC:20750): (zinc finger DHHC-type palmitoyltransferase 21) Enables palmitoyltransferase activity. Involved in peptidyl-L-cysteine S-palmitoylation. Located in Golgi apparatus and plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

ZDHHC21 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.888

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZDHHC21	NM_178566.6 linkuse as main transcript	c.362C>A	p.Pro121Gln	missense_variant	6/10	ENST00000380916.9	NP_848661.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZDHHC21	ENST00000380916.9 linkuse as main transcript	c.362C>A	p.Pro121Gln	missense_variant	6/10	1	NM_178566.6	ENSP00000370303	P1

Frequencies

GnomAD3 genomes

AF:

0.0000789

AC:

AN:

152060

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000290

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000289

AC:

AN:

242336

Hom.:

AF XY:

0.0000305

AC XY:

AN XY:

131002

show subpopulations

Gnomad AFR exome

AF:

0.000374

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:

0.00000900

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000693

AC:

AN:

1444038

Hom.:

Cov.:

AF XY:

0.00000696

AC XY:

AN XY:

718668

show subpopulations

Gnomad4 AFR exome

AF:

0.000244

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:

9.07e-7

Gnomad4 OTH exome

AF:

0.0000168

GnomAD4 genome

AF:

0.0000789

AC:

AN:

152060

Hom.:

Cov.:

AF XY:

0.0000808

AC XY:

AN XY:

74252

show subpopulations

Gnomad4 AFR

AF:

0.000290

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000164

Hom.:

Bravo

AF:

0.0000869

ESP6500AA

AF:

0.000454

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.0000247

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Apr 27, 2024

The c.362C>A (p.P121Q) alteration is located in exon 6 (coding exon 3) of the ZDHHC21 gene. This alteration results from a C to A substitution at nucleotide position 362, causing the proline (P) at amino acid position 121 to be replaced by a glutamine (Q). 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

0.97

BayesDel_addAF

Uncertain

0.044

BayesDel_noAF

Pathogenic

0.14

CADD

Pathogenic

DANN

Uncertain

0.99

DEOGEN2

Uncertain

0.56

Eigen

Pathogenic

1.0

Eigen_PC

Pathogenic

0.98

FATHMM_MKL

Uncertain

0.96

LIST_S2

Uncertain

0.94

M_CAP

Benign

0.029

MetaRNN

Pathogenic

0.89

MetaSVM

Benign

-0.65

MutationAssessor

Pathogenic

3.1

MutationTaster

Benign

1.0

PrimateAI

Pathogenic

0.80

PROVEAN

Pathogenic

-7.9

REVEL

Uncertain

0.63

Sift

Pathogenic

0.0

Sift4G

Pathogenic

0.0

Polyphen

1.0

Vest4

0.84

MVP

0.61

MPC

0.61

ClinPred

0.86

GERP RS

6.1

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.83

gMVP

0.84

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