NM_001320466.2:c.7C>T

Variant names:

• chr3-113948809-C-T
• rs541860562
• NM_001320466.2:c.7C>T

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_001320466.2(ZDHHC23):​c.7C>T​(p.Gln3*) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,866 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: ZDHHC23 NM_001320466.2 stop_gained
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.00
• 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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

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.7C>T	p.Gln3*	stop_gained	Exon 2 of 5	NP_001307395.1	A0A1W2PRJ8
	ZDHHC23	NM_001320467.2		c.7C>T	p.Gln3*	stop_gained	Exon 2 of 5	NP_001307396.1	A0A1W2PRJ8
	ZDHHC23	NM_001320468.2		c.7C>T	p.Gln3*	stop_gained	Exon 2 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.7C>T	p.Gln3*	stop_gained	Exon 2 of 5	ENSP00000492287.2	A0A1W2PRJ8
	ZDHHC23	ENST00000330212.7	TSL:1	c.7C>T	p.Gln3*	stop_gained	Exon 2 of 6	ENSP00000330485.3	Q8IYP9
	ZDHHC23	ENST00000869326.1		c.7C>T	p.Gln3*	stop_gained	Exon 2 of 5	ENSP00000539385.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461866 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 727240

African (AFR) AF: 0.00 AC: 0 AN: 33470

American (AMR) AF: 0.00 AC: 0 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26134

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86254

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53420

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5764

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1112010

Other (OTH) AF: 0.00 AC: 0 AN: 60394

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Pathogenic	0.38	D
BayesDel_noAF	Pathogenic	0.31
CADD	Pathogenic	34
DANN	Uncertain	1.0
Eigen	Uncertain	0.36
Eigen_PC	Benign	0.11
FATHMM_MKL	Benign	0.28	N
PhyloP100		1.0
Vest4		0.054
GERP RS		5.0
PromoterAI		-0.0080	Neutral
Mutation Taster		=105/95	disease causing (fs/PTC)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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

dbSNP: rs541860562; hg19: chr3-113667656;