10-112430856-G-T

Position:

• chr10-112430856-G-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_022494.3(ZDHHC6):​c.1190C>A​(p.Pro397His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,554 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 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: 6.8e-7 (0 hom.)
• Consequence: ZDHHC6 NM_022494.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.45

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]

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.036509037).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZDHHC6	NM_022494.3	c.1190C>A	p.Pro397His	missense_variant	11/11	ENST00000369405.7	NP_071939.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZDHHC6	ENST00000369405.7	c.1190C>A	p.Pro397His	missense_variant	11/11	1	NM_022494.3	ENSP00000358413	P4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461554 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 727068

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.0000224

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: 0.00

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

Apr 07, 2023

The c.1190C>A (p.P397H) alteration is located in exon 11 (coding exon 10) of the ZDHHC6 gene. This alteration results from a C to A substitution at nucleotide position 1190, causing the proline (P) at amino acid position 397 to be replaced by a histidine (H). 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	0.083
BayesDel_addAF	Benign	-0.30	T
BayesDel_noAF	Benign	-0.67
CADD	Benign	22
DANN	Benign	0.91
DEOGEN2	Benign	0.0061	T;.
Eigen	Benign	-0.20
Eigen_PC	Benign	0.042
FATHMM_MKL	Uncertain	0.81	D
LIST_S2	Benign	0.77	T;T
M_CAP	Benign	0.0020	T
MetaRNN	Benign	0.037	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-0.34	N;.
MutationTaster	Benign	0.88	N;N
PrimateAI	Benign	0.39	T
PROVEAN	Benign	-0.70	N;N
REVEL	Benign	0.068
Sift	Benign	0.28	T;T
Sift4G	Benign	0.37	T;T
Polyphen		0.0	B;B
Vest4		0.092
MutPred		0.26		Gain of helix (P = 0.0425);.;
MVP		0.085
MPC		0.15
ClinPred		0.71	D
GERP RS		3.9
Varity_R		0.065
gMVP		0.34

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: chr10-114190614;