10-112440668-T-C
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Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_022494.3(ZDHHC6):āc.547A>Gā(p.Ile183Val) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000496 in 1,613,692 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 (ā ).
Frequency
Genomes: š 0.000072 ( 0 hom., cov: 33)
Exomes š: 0.000047 ( 0 hom. )
Consequence
ZDHHC6
NM_022494.3 missense
NM_022494.3 missense
Scores
1
5
13
Clinical Significance
Conservation
PhyloP100: 7.99
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]
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ACMG classification
Classification made for transcript
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=0.1891886).
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes AF: 0.0000723 AC: 11AN: 152176Hom.: 0 Cov.: 33
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GnomAD3 exomes AF: 0.0000756 AC: 19AN: 251306Hom.: 0 AF XY: 0.0000810 AC XY: 11AN XY: 135810
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GnomAD4 exome AF: 0.0000472 AC: 69AN: 1461516Hom.: 0 Cov.: 33 AF XY: 0.0000578 AC XY: 42AN XY: 727078
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GnomAD4 genome AF: 0.0000723 AC: 11AN: 152176Hom.: 0 Cov.: 33 AF XY: 0.0000807 AC XY: 6AN XY: 74338
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Jan 24, 2023 | The c.547A>G (p.I183V) alteration is located in exon 5 (coding exon 4) of the ZDHHC6 gene. This alteration results from a A to G substitution at nucleotide position 547, causing the isoleucine (I) at amino acid position 183 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Benign
DANN
Uncertain
DEOGEN2
Benign
.;T;.
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Pathogenic
D
LIST_S2
Uncertain
D;D;D
M_CAP
Benign
T
MetaRNN
Benign
T;T;T
MetaSVM
Benign
T
MutationAssessor
Benign
.;N;.
PrimateAI
Uncertain
T
PROVEAN
Benign
.;N;N
REVEL
Benign
Sift
Benign
.;T;T
Sift4G
Benign
T;T;T
Polyphen
0.99, 0.38
.;D;B
Vest4
MVP
MPC
0.31
ClinPred
T
GERP RS
Varity_R
gMVP
Splicing
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Calibrated prediction
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SpliceAI score (max)
Details are displayed if max score is > 0.2
DS_AL_spliceai
Position offset: 27
Find out detailed SpliceAI scores and Pangolin per-transcript scores at