3-113954212-C-T

Variant names:

• chr3-113954212-C-T
• rs147787442
• NM_001320466.2:c.674C>T

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_001320466.2(ZDHHC23):​c.674C>T​(p.Pro225Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000149 in 1,614,046 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00011 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00015 (0 hom.)
• Consequence: ZDHHC23 NM_001320466.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.20
• Publications: 4 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: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.03956291).

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.674C>T	p.Pro225Leu	missense	Exon 3 of 5	NP_001307395.1	A0A1W2PRJ8
	ZDHHC23	NM_001320467.2		c.674C>T	p.Pro225Leu	missense	Exon 3 of 5	NP_001307396.1	A0A1W2PRJ8
	ZDHHC23	NM_001320468.2		c.674C>T	p.Pro225Leu	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.674C>T	p.Pro225Leu	missense	Exon 3 of 5	ENSP00000492287.2	A0A1W2PRJ8
	ZDHHC23	ENST00000330212.7	TSL:1	c.674C>T	p.Pro225Leu	missense	Exon 3 of 6	ENSP00000330485.3	Q8IYP9
	ZDHHC23	ENST00000869326.1		c.674C>T	p.Pro225Leu	missense	Exon 3 of 5	ENSP00000539385.1

Frequencies

GnomAD3 genomes AF: 0.000105 AC: 16 AN: 152170 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000121

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: 0.000162

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000637 AC: 16 AN: 251286 AF XY: 0.0000663

Gnomad AFR exome AF: 0.000185

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000106

Gnomad OTH exome AF: 0.000163

GnomAD4 exome AF: 0.000153 AC: 224 AN: 1461876 Hom.: 0 Cov.: 30 AF XY: 0.000144 AC XY: 105 AN XY: 727238

African (AFR) AF: 0.0000299 AC: 1 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26130

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.0000116 AC: 1 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53412

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.000192 AC: 214 AN: 1112008

Other (OTH) AF: 0.000132 AC: 8 AN: 60396

GnomAD4 genome AF: 0.000105 AC: 16 AN: 152170 Hom.: 0 Cov.: 32 AF XY: 0.0000942 AC XY: 7 AN XY: 74344

African (AFR) AF: 0.000121 AC: 5 AN: 41450

American (AMR) AF: 0.00 AC: 0 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5190

South Asian (SAS) AF: 0.00 AC: 0 AN: 4826

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10608

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.000162 AC: 11 AN: 68024

Other (OTH) AF: 0.00 AC: 0 AN: 2094

Alfa AF: 0.000164 Hom.: 0

Bravo AF: 0.000147

ESP6500AA AF: 0.000454 AC: 2

ESP6500EA AF: 0.00 AC: 0

ExAC AF: 0.0000576 AC: 7

EpiCase AF: 0.0000545

EpiControl AF: 0.000119

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	Benign	0.070
BayesDel_addAF	Benign	-0.49	T
BayesDel_noAF	Benign	-0.66
CADD	Benign	14
DANN	Benign	0.25
DEOGEN2	Benign	0.031	T
Eigen	Benign	-0.86
Eigen_PC	Benign	-0.81
FATHMM_MKL	Benign	0.12	N
LIST_S2	Benign	0.77	T
M_CAP	Benign	0.0067	T
MetaRNN	Benign	0.040	T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	1.1	L
PhyloP100		1.2
PrimateAI	Benign	0.27	T
PROVEAN	Benign	-0.80	N
REVEL	Benign	0.032
Sift	Benign	0.67	T
Sift4G	Benign	0.67	T
Polyphen		0.0	B
Vest4		0.082
MVP		0.030
MPC		0.20
ClinPred		0.023	T
GERP RS		2.8
Varity_R		0.043
Mutation Taster		=97/3	polymorphism

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

dbSNP: rs147787442; hg19: chr3-113673059;