chr9-128721258-A-G

Position:

• chr9-128721258-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_032799.5(ZDHHC12):​c.727T>C​(p.Phe243Leu) variant causes a missense change. The variant allele was found at a frequency of 0.00000206 in 1,453,110 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 (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: ZDHHC12 NM_032799.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.09

Genes affected

ZDHHC12 (HGNC:19159): (zinc finger DHHC-type palmitoyltransferase 12) Enables palmitoyltransferase activity. Involved in protein palmitoylation. Located in Golgi apparatus and endoplasmic reticulum. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.38937625).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZDHHC12	NM_032799.5	c.727T>C	p.Phe243Leu	missense_variant	5/5	ENST00000372663.9	NP_116188.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZDHHC12	ENST00000372663.9	c.727T>C	p.Phe243Leu	missense_variant	5/5	1	NM_032799.5	ENSP00000361748.4
ZDHHC12	ENST00000372667.9	c.769T>C	p.Phe257Leu	missense_variant	5/5	5		ENSP00000361752.5
ZDHHC12	ENST00000467312.1	n.2158T>C		non_coding_transcript_exon_variant	4/4	2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000206 AC: 3 AN: 1453110 Hom.: 0 Cov.: 30 AF XY: 0.00000139 AC XY: 1 AN XY: 721964

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000271

Gnomad4 OTH exome AF: 0.00

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 22, 2023

The c.727T>C (p.F243L) alteration is located in exon 5 (coding exon 5) of the ZDHHC12 gene. This alteration results from a T to C substitution at nucleotide position 727, causing the phenylalanine (F) at amino acid position 243 to be replaced by a leucine (L). 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	0.75
BayesDel_addAF	Pathogenic	0.18	D
BayesDel_noAF	Uncertain	0.020
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.028	T;T
Eigen	Uncertain	0.39
Eigen_PC	Uncertain	0.41
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Benign	0.76	T;T
M_CAP	Benign	0.032	D
MetaRNN	Benign	0.39	T;T
MetaSVM	Benign	-0.94	T
MutationAssessor	Uncertain	2.2	M;.
PrimateAI	Uncertain	0.70	T
PROVEAN	Benign	-2.2	N;N
REVEL	Uncertain	0.29
Sift	Benign	0.37	T;T
Sift4G	Benign	0.38	T;T
Polyphen		0.99	D;.
Vest4		0.46
MutPred		0.68		Gain of catalytic residue at F243 (P = 0.0227);.;
MVP		0.45
MPC		0.75
ClinPred		0.98	D
GERP RS		4.9
Varity_R		0.30
gMVP		0.64

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: chr9-131483537;