22-20139817-T-C

Position:

• chr22-20139817-T-C

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_013373.4(ZDHHC8):​c.482T>C​(p.Val161Ala) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: ZDHHC8 NM_013373.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.58

Genes affected

ZDHHC8 (HGNC:18474): (zinc finger DHHC-type palmitoyltransferase 8) This gene encodes a four transmembrane protein that is a member of the zinc finger DHHC domain-containing protein family. The encoded protein may function as a palmitoyltransferase. Defects in this gene may be associated with a susceptibility to schizophrenia. Alternate splicing of this gene results in multiple transcript variants. A pseudogene of this gene is found on chromosome 22.[provided by RefSeq, May 2010]

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.4119602).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZDHHC8	NM_013373.4	c.482T>C	p.Val161Ala	missense_variant	4/11	ENST00000334554.12	NP_037505.1
ZDHHC8	NM_001185024.2	c.482T>C	p.Val161Ala	missense_variant	4/11		NP_001171953.1
ZDHHC8	XM_006724239.3	c.482T>C	p.Val161Ala	missense_variant	4/12		XP_006724302.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZDHHC8	ENST00000334554.12	c.482T>C	p.Val161Ala	missense_variant	4/11	1	NM_013373.4	ENSP00000334490.7

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 33

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 22, 2024

The c.482T>C (p.V161A) alteration is located in exon 4 (coding exon 4) of the ZDHHC8 gene. This alteration results from a T to C substitution at nucleotide position 482, causing the valine (V) at amino acid position 161 to be replaced by an alanine (A). 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	0.14
BayesDel_addAF	Benign	-0.063	T
BayesDel_noAF	Benign	-0.33
CADD	Uncertain	25
DANN	Uncertain	0.98
DEOGEN2	Benign	0.41	.;T;.
Eigen	Benign	0.054
Eigen_PC	Benign	0.15
FATHMM_MKL	Uncertain	0.97	D
LIST_S2	Uncertain	0.87	D;D;D
M_CAP	Benign	0.026	D
MetaRNN	Benign	0.41	T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.0	.;L;L
PrimateAI	Pathogenic	0.84	D
PROVEAN	Uncertain	-2.5	D;N;N
REVEL	Benign	0.20
Sift	Benign	0.20	T;D;T
Sift4G	Benign	0.097	T;D;D
Polyphen		0.0040, 0.86	.;B;P
Vest4		0.62, 0.62
MutPred		0.54		.;Loss of stability (P = 0.1387);Loss of stability (P = 0.1387);
MVP		0.082
MPC		1.2
ClinPred		0.76	D
GERP RS		3.5
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.16
gMVP		0.93

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr22-20127340;