rs1376399350

Variant names:

• chr8-17156790-G-C
• rs1376399350
• NM_016353.5:c.67G>C

Your query was ambiguous. Multiple possible variants found:

• chr8-17156790-G-C
• chr8-17156790-G-T
• chr8-17156790-G-A

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_016353.5(ZDHHC2):​c.67G>C​(p.Val23Leu) variant causes a missense change. The variant allele was found at a frequency of 0.00000073 in 1,370,570 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 7.3e-7 (0 hom.)
• Consequence: ZDHHC2 NM_016353.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.08
• Publications: 0 publications found

Genes affected

ZDHHC2 (HGNC:18469): (zinc finger DHHC-type palmitoyltransferase 2) Enables protein homodimerization activity and protein-cysteine S-palmitoyltransferase activity. Involved in several processes, including peptidyl-L-cysteine S-palmitoylation; regulation of protein catabolic process; and regulation of protein localization to plasma membrane. Located in Golgi apparatus and endoplasmic reticulum membrane. [provided by Alliance of Genome Resources, Apr 2022]

ENSG00000298219 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.38964254).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_016353.5. 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
	ZDHHC2	NM_016353.5	MANE Select	c.67G>C	p.Val23Leu	missense	Exon 1 of 13	NP_057437.1	Q9UIJ5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZDHHC2	ENST00000262096.13	TSL:1 MANE Select	c.67G>C	p.Val23Leu	missense	Exon 1 of 13	ENSP00000262096.8	Q9UIJ5
	ZDHHC2	ENST00000955296.1		c.67G>C	p.Val23Leu	missense	Exon 1 of 15	ENSP00000625355.1
	ZDHHC2	ENST00000955297.1		c.67G>C	p.Val23Leu	missense	Exon 1 of 12	ENSP00000625356.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 7.30e-7 AC: 1 AN: 1370570 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 675916

African (AFR) AF: 0.00 AC: 0 AN: 28982

American (AMR) AF: 0.00 AC: 0 AN: 33022

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24358

East Asian (EAS) AF: 0.00 AC: 0 AN: 33090

South Asian (SAS) AF: 0.00 AC: 0 AN: 76716

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 46170

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5490

European-Non Finnish (NFE) AF: 9.38e-7 AC: 1 AN: 1066058

Other (OTH) AF: 0.00 AC: 0 AN: 56684

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	0.87
BayesDel_addAF	Benign	-0.081	T
BayesDel_noAF	Benign	-0.35
CADD	Benign	23
DANN	Benign	0.97
DEOGEN2	Benign	0.17	T
Eigen	Benign	-0.25
Eigen_PC	Benign	-0.29
FATHMM_MKL	Benign	0.68	D
LIST_S2	Uncertain	0.87	D
M_CAP	Pathogenic	0.96	D
MetaRNN	Benign	0.39	T
MetaSVM	Benign	-0.48	T
MutationAssessor	Uncertain	2.9	M
PhyloP100		5.1
PrimateAI	Pathogenic	0.86	D
PROVEAN	Benign	-2.1	N
REVEL	Benign	0.21
Sift	Uncertain	0.0010	D
Sift4G	Uncertain	0.016	D
Polyphen		0.018	B
Vest4		0.29
MutPred		0.44		Gain of helix (P = 0.0696)
MVP		0.36
MPC		0.021
ClinPred		0.60	D
GERP RS		1.7
PromoterAI		-0.054	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Varity_R		0.29
gMVP		0.80
Mutation Taster		=74/26	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: rs1376399350; hg19: chr8-17014299;