chr12-76846663-T-G

Position:

• chr12-76846663-T-G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_015336.4(ZDHHC17):​c.1491T>G​(p.Ile497Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,457,766 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: ZDHHC17 NM_015336.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.441

Genes affected

ZDHHC17 (HGNC:18412): (zinc finger DHHC-type palmitoyltransferase 17) Enables identical protein binding activity and protein-cysteine S-palmitoyltransferase activity. Involved in lipoprotein transport and protein palmitoylation. Located in Golgi membrane; Golgi-associated vesicle membrane; and aggresome. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.1396999).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ZDHHC17	NM_015336.4	c.1491T>G	p.Ile497Met	missense_variant	14/17	ENST00000426126.7
ZDHHC17	NM_001359626.1	c.1461T>G	p.Ile487Met	missense_variant	14/17

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ZDHHC17	ENST00000426126.7	c.1491T>G	p.Ile497Met	missense_variant	14/17	1	NM_015336.4	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1457766 Hom.: 0 Cov.: 30 AF XY: 0.00000138 AC XY: 1 AN XY: 724752

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: 0.0000234

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

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

Sep 01, 2021

The c.1491T>G (p.I497M) alteration is located in exon 14 (coding exon 14) of the ZDHHC17 gene. This alteration results from a T to G substitution at nucleotide position 1491, causing the isoleucine (I) at amino acid position 497 to be replaced by a methionine (M). 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	0.067
BayesDel_addAF	Benign	-0.17	T
BayesDel_noAF	Benign	-0.48
CADD	Benign	17
DANN	Benign	0.86
DEOGEN2	Benign	0.13	T
Eigen	Benign	-0.24
Eigen_PC	Benign	-0.086
FATHMM_MKL	Uncertain	0.79	D
LIST_S2	Uncertain	0.86	D
M_CAP	Benign	0.0077	T
MetaRNN	Benign	0.14	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.5	L
MutationTaster	Benign	1.0	D;D
PrimateAI	Uncertain	0.72	T
PROVEAN	Benign	-0.76	N
REVEL	Benign	0.078
Sift	Benign	0.18	T
Sift4G	Benign	0.42	T
Polyphen		0.0020	B
Vest4		0.33
MutPred		0.48		Loss of catalytic residue at I497 (P = 0.0255);
MVP		0.068
MPC		0.40
ClinPred		0.39	T
GERP RS		4.3
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.12
gMVP		0.79

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: chr12-77240443;