chr16-67394695-C-A

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate

The NM_001323627.2(ZDHHC1):​c.1364G>T​(p.Arg455Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000878 in 1,138,362 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 Likely benign (★).

Frequency

Genomes: not found (cov: 33)
Exomes 𝑓: 8.8e-7 ( 0 hom. )

Consequence

ZDHHC1
NM_001323627.2 missense

Scores

1
18

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.315
Variant links:
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.03076917).
BP6
Variant 16-67394695-C-A is Benign according to our data. Variant chr16-67394695-C-A is described in ClinVar as [Likely_benign]. Clinvar id is 3334208.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
ZDHHC1NM_001323627.2 linkuse as main transcriptc.1364G>T p.Arg455Leu missense_variant 12/12 ENST00000565726.3 NP_001310556.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
ZDHHC1ENST00000565726.3 linkuse as main transcriptc.1364G>T p.Arg455Leu missense_variant 12/125 NM_001323627.2 ENSP00000459264 P1
ZDHHC1ENST00000348579.6 linkuse as main transcriptc.1429G>T p.Gly477Cys missense_variant 11/111 ENSP00000340299
ZDHHC1ENST00000566075.1 linkuse as main transcriptn.919G>T non_coding_transcript_exon_variant 5/53

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
AF:
8.78e-7
AC:
1
AN:
1138362
Hom.:
0
Cov.:
31
AF XY:
0.00000182
AC XY:
1
AN XY:
550024
show subpopulations
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:
0.0000278
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
33

ClinVar

Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Benign:1
Likely benign, criteria provided, single submitterclinical testingAmbry GeneticsMay 30, 2024This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.080
BayesDel_addAF
Benign
-0.24
T
BayesDel_noAF
Benign
-0.58
CADD
Benign
6.2
DANN
Benign
0.85
DEOGEN2
Benign
0.0077
T
Eigen
Benign
-1.3
Eigen_PC
Benign
-1.1
FATHMM_MKL
Benign
0.0083
N
LIST_S2
Benign
0.31
T
M_CAP
Benign
0.036
D
MetaRNN
Benign
0.031
T
MetaSVM
Benign
-1.1
T
MutationAssessor
Benign
0.0
N
MutationTaster
Benign
1.0
N
PrimateAI
Uncertain
0.59
T
PROVEAN
Benign
0.44
N
REVEL
Benign
0.069
Sift
Benign
1.0
T
Sift4G
Benign
0.17
T
Polyphen
0.0
B
Vest4
0.12
MutPred
0.13
Loss of relative solvent accessibility (P = 0.0306);
MVP
0.040
MPC
1.5
ClinPred
0.038
T
GERP RS
0.96
Varity_R
0.066
gMVP
0.13

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: chr16-67428598; API