chr3-113954006-C-A

Variant names:

• chr3-113954006-C-A
• NM_001320466.2:c.468C>A

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2 PP3

The NM_001320466.2(ZDHHC23):​c.468C>A​(p.Phe156Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: ZDHHC23 NM_001320466.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.42
• Publications: 0 publications found

Genes affected

ZDHHC23 (HGNC:28654): (zinc finger DHHC-type palmitoyltransferase 23) Predicted to enable protein-cysteine S-palmitoyltransferase activity. Involved in protein localization to plasma membrane and protein palmitoylation. Predicted to be located in Golgi membrane. Predicted to be integral component of membrane. Predicted to be active in Golgi apparatus and endoplasmic reticulum. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Uncertain_significance. The variant received 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.829

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001320466.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZDHHC23	NM_001320466.2	MANE Select	c.468C>A	p.Phe156Leu	missense	Exon 3 of 5	NP_001307395.1	A0A1W2PRJ8
	ZDHHC23	NM_001320467.2		c.468C>A	p.Phe156Leu	missense	Exon 3 of 5	NP_001307396.1	A0A1W2PRJ8
	ZDHHC23	NM_001320468.2		c.468C>A	p.Phe156Leu	missense	Exon 3 of 5	NP_001307397.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZDHHC23	ENST00000638807.2	TSL:5 MANE Select	c.468C>A	p.Phe156Leu	missense	Exon 3 of 5	ENSP00000492287.2	A0A1W2PRJ8
	ZDHHC23	ENST00000330212.7	TSL:1	c.468C>A	p.Phe156Leu	missense	Exon 3 of 6	ENSP00000330485.3	Q8IYP9
	ZDHHC23	ENST00000869326.1		c.468C>A	p.Phe156Leu	missense	Exon 3 of 5	ENSP00000539385.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.98
BayesDel_addAF	Pathogenic	0.28	D
BayesDel_noAF	Pathogenic	0.17
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.27	T
Eigen	Uncertain	0.55
Eigen_PC	Uncertain	0.50
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Uncertain	0.91	D
M_CAP	Benign	0.065	D
MetaRNN	Pathogenic	0.83	D
MetaSVM	Uncertain	-0.17	T
MutationAssessor	Uncertain	2.6	M
PhyloP100		2.4
PrimateAI	Uncertain	0.79	T
PROVEAN	Pathogenic	-4.6	D
REVEL	Uncertain	0.59
Sift	Uncertain	0.0050	D
Sift4G	Uncertain	0.0080	D
Polyphen		1.0	D
Vest4		0.91
MutPred		0.63		Loss of sheet (P = 0.0315)
MVP		0.33
MPC		0.81
ClinPred		1.0	D
GERP RS		3.9
Varity_R		0.60
Mutation Taster		=22/78	disease causing

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

Other links and lift over

hg19: chr3-113672853;