chr16-67395018-G-A
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Variant summary
Our verdict is Likely benign. Variant got -3 ACMG points: 2P and 5B. PM2BP4_StrongBP7
The NM_001323627.2(ZDHHC1):c.1149C>T(p.Thr383=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000018 in 1,611,662 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: 𝑓 0.000020 ( 0 hom., cov: 33)
Exomes 𝑓: 0.000018 ( 0 hom. )
Consequence
ZDHHC1
NM_001323627.2 synonymous
NM_001323627.2 synonymous
Scores
3
16
Clinical Significance
Conservation
PhyloP100: 0.309
Genes affected
ZDHHC1 (HGNC:17916): (zinc finger DHHC-type containing 1) Enables palmitoyltransferase activity. Involved in antiviral innate immune response; positive regulation of defense response to virus by host; and protein palmitoylation. Located in Golgi apparatus and endoplasmic reticulum membrane. [provided by Alliance of Genome Resources, Apr 2022]
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ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -3 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.06215918).
BP7
Synonymous conserved (PhyloP=0.309 with no splicing effect.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
ZDHHC1 | NM_001323627.2 | c.1149C>T | p.Thr383= | synonymous_variant | 11/12 | ENST00000565726.3 | NP_001310556.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
ZDHHC1 | ENST00000348579.6 | c.1214C>T | p.Pro405Leu | missense_variant | 10/11 | 1 | ENSP00000340299 | |||
ZDHHC1 | ENST00000565726.3 | c.1149C>T | p.Thr383= | synonymous_variant | 11/12 | 5 | NM_001323627.2 | ENSP00000459264 | P1 | |
ZDHHC1 | ENST00000566075.1 | n.704C>T | non_coding_transcript_exon_variant | 4/5 | 3 |
Frequencies
GnomAD3 genomes AF: 0.0000197 AC: 3AN: 152238Hom.: 0 Cov.: 33
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GnomAD3 exomes AF: 0.0000163 AC: 4AN: 245910Hom.: 0 AF XY: 0.0000224 AC XY: 3AN XY: 133782
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GnomAD4 exome AF: 0.0000178 AC: 26AN: 1459424Hom.: 0 Cov.: 31 AF XY: 0.0000193 AC XY: 14AN XY: 725892
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GnomAD4 genome AF: 0.0000197 AC: 3AN: 152238Hom.: 0 Cov.: 33 AF XY: 0.0000269 AC XY: 2AN XY: 74372
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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 | Dec 16, 2023 | The c.1214C>T (p.P405L) alteration is located in exon 10 (coding exon 9) of the ZDHHC1 gene. This alteration results from a C to T substitution at nucleotide position 1214, causing the proline (P) at amino acid position 405 to be replaced by a leucine (L). 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
Benign
DEOGEN2
Benign
T
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Benign
N
LIST_S2
Benign
T
M_CAP
Benign
D
MetaRNN
Benign
T
MetaSVM
Benign
T
MutationAssessor
Benign
N
MutationTaster
Benign
N
PrimateAI
Uncertain
T
PROVEAN
Benign
N
REVEL
Benign
Sift
Uncertain
D
Sift4G
Uncertain
D
Polyphen
B
Vest4
MutPred
Loss of loop (P = 0.0145);
MVP
MPC
ClinPred
T
GERP RS
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gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at