10-112432480-G-C

Position:

• chr10-112432480-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM1 PM2

The NM_022494.3(ZDHHC6):​c.987C>G​(p.Cys329Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: ZDHHC6 NM_022494.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.23

Genes affected

ZDHHC6 (HGNC:19160): (zinc finger DHHC-type palmitoyltransferase 6) Enables palmitoyltransferase activity. Involved in positive regulation of mitochondrial fusion and protein palmitoylation. Located in endoplasmic reticulum. [provided by Alliance of Genome Resources, Apr 2022]

ZDHHC6 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 4 ACMG points.

• PM1: In a lipid_moiety_binding_region S-palmitoyl cysteine (size 0) in uniprot entity ZDHC6_HUMAN
• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZDHHC6	NM_022494.3	c.987C>G	p.Cys329Trp	missense_variant	9/11	ENST00000369405.7	NP_071939.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZDHHC6	ENST00000369405.7	c.987C>G	p.Cys329Trp	missense_variant	9/11	1	NM_022494.3	ENSP00000358413.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

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

Aug 21, 2024

The c.987C>G (p.C329W) alteration is located in exon 9 (coding exon 8) of the ZDHHC6 gene. This alteration results from a C to G substitution at nucleotide position 987, causing the cysteine (C) at amino acid position 329 to be replaced by a tryptophan (W). 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	Pathogenic	0.60
BayesDel_addAF	Pathogenic	0.18	D
BayesDel_noAF	Uncertain	0.020
CADD	Benign	22
DANN	Uncertain	0.99
DEOGEN2	Benign	0.021	.;T;.
Eigen	Benign	0.15
Eigen_PC	Benign	0.091
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Uncertain	0.94	D;D;D
M_CAP	Uncertain	0.088	D
MetaRNN	Uncertain	0.72	D;D;D
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.7	.;M;.
PrimateAI	Uncertain	0.75	T
PROVEAN	Benign	-2.0	.;N;N
REVEL	Uncertain	0.36
Sift	Uncertain	0.022	.;D;D
Sift4G	Uncertain	0.057	T;T;T
Polyphen		0.98, 0.99	.;D;D
Vest4		0.83
MutPred		0.69		Gain of loop (P = 0.0097);Gain of loop (P = 0.0097);.;
MVP		0.12
MPC		0.20
ClinPred		0.91	D
GERP RS		0.62
Varity_R		0.27
gMVP		0.91

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr10-114192238;