chr3-113954367-A-G

Position:

• chr3-113954367-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001320466.2(ZDHHC23):​c.829A>G​(p.Ile277Val) 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 benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. I277M) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 33)
• Consequence: ZDHHC23 NM_001320466.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.88

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

Verdict is Uncertain_significance. Variant got 2 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ZDHHC23	NM_001320466.2	c.829A>G	p.Ile277Val	missense_variant	3/5	ENST00000638807.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ZDHHC23	ENST00000638807.2	c.829A>G	p.Ile277Val	missense_variant	3/5	5	NM_001320466.2	P1
ZDHHC23	ENST00000330212.7	c.829A>G	p.Ile277Val	missense_variant	3/6	1
ZDHHC23	ENST00000498275.5	c.811A>G	p.Ile271Val	missense_variant	4/7	2
ZDHHC23	ENST00000478793.1	c.829A>G	p.Ile277Val	missense_variant, NMD_transcript_variant	3/7	2

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

May 24, 2023

The c.829A>G (p.I277V) alteration is located in exon 3 (coding exon 2) of the ZDHHC23 gene. This alteration results from a A to G substitution at nucleotide position 829, causing the isoleucine (I) at amino acid position 277 to be replaced by a valine (V). 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	0.20
BayesDel_addAF	Benign	-0.16	T
BayesDel_noAF	Benign	-0.47
CADD	Benign	22
DANN	Uncertain	0.98
DEOGEN2	Benign	0.032	T;T;.
Eigen	Benign	-0.065
Eigen_PC	Benign	-0.00035
FATHMM_MKL	Uncertain	0.89	D
LIST_S2	Uncertain	0.94	D;D;D
M_CAP	Benign	0.0077	T
MetaRNN	Benign	0.30	T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.1	L;.;.
MutationTaster	Benign	1.0	D;D
PrimateAI	Uncertain	0.61	T
PROVEAN	Benign	-0.47	N;N;.
REVEL	Benign	0.049
Sift	Uncertain	0.023	D;D;.
Sift4G	Benign	0.17	T;T;.
Polyphen		0.68	P;.;.
Vest4		0.20
MutPred		0.47		Gain of MoRF binding (P = 0.1159);.;.;
MVP		0.067
MPC		0.28
ClinPred		0.34	T
GERP RS		1.8
Varity_R		0.042

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.40		Details are displayed if max score is > 0.2
DS_DG_spliceai		0.40		Position offset: -1

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: chr3-113673214;