16-84979278-T-C

Position:

• chr16-84979278-T-C

Variant summary

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

The ENST00000313732.9(ZDHHC7):​c.448A>G​(p.Lys150Glu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000686 in 1,457,210 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: 6.9e-7 (0 hom.)
• Consequence: ZDHHC7 ENST00000313732.9 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.86

Genes affected

ZDHHC7 (HGNC:18459): (zinc finger DHHC-type palmitoyltransferase 7) Enables protein-cysteine S-palmitoyltransferase activity. Involved in several processes, including peptidyl-L-cysteine S-palmitoylation; polarized epithelial cell differentiation; and regulation of signal transduction. Located in Golgi apparatus and nucleoplasm. [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=0.41574484).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZDHHC7	NM_017740.3	c.448A>G	p.Lys150Glu	missense_variant	5/8	ENST00000313732.9	NP_060210.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZDHHC7	ENST00000313732.9	c.448A>G	p.Lys150Glu	missense_variant	5/8	1	NM_017740.3	ENSP00000315604	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.86e-7 AC: 1 AN: 1457210 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 724822

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000253

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

Bravo AF: 0.0000189

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 17, 2023

The c.559A>G (p.K187E) alteration is located in exon 6 (coding exon 4) of the ZDHHC7 gene. This alteration results from a A to G substitution at nucleotide position 559, causing the lysine (K) at amino acid position 187 to be replaced by a glutamic acid (E). 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	0.65
BayesDel_addAF	Uncertain	0.065	T
BayesDel_noAF	Benign	-0.15
CADD	Uncertain	25
DANN	Benign	0.94
DEOGEN2	Benign	0.026	T;.;.
Eigen	Benign	-0.30
Eigen_PC	Benign	-0.18
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Uncertain	0.88	D;D;D
M_CAP	Benign	0.022	T
MetaRNN	Benign	0.42	T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.2	L;.;.
MutationTaster	Benign	1.0	D;D
PrimateAI	Pathogenic	0.85	D
PROVEAN	Benign	-1.2	N;N;N
REVEL	Benign	0.25
Sift	Benign	0.12	T;T;T
Sift4G	Benign	0.15	T;T;T
Polyphen		0.023	B;B;.
Vest4		0.77
MutPred		0.53		Loss of methylation at K150 (P = 2e-04);.;.;
MVP		0.061
MPC		0.69
ClinPred		0.88	D
GERP RS		4.3
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.22
gMVP		0.80

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs1327513670; hg19: chr16-85012884;