3-44959150-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001135179.2(ZDHHC3):​c.287G>A​(p.Arg96Gln) variant causes a missense change. The variant allele was found at a frequency of 0.0000116 in 1,461,872 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 0.000012 ( 0 hom. )

Consequence

ZDHHC3
NM_001135179.2 missense

Scores

1
8
9

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.64
Variant links:
Genes affected
ZDHHC3 (HGNC:18470): (zinc finger DHHC-type palmitoyltransferase 3) Enables palmitoyltransferase activity. Involved in several processes, including TRAIL-activated apoptotic signaling pathway; protein localization to membrane; and protein localization to photoreceptor outer segment. Located in Golgi apparatus. [provided by Alliance of Genome Resources, Apr 2022]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
ZDHHC3NM_001135179.2 linkc.287G>A p.Arg96Gln missense_variant 2/7 ENST00000424952.7 NP_001128651.1 Q9NYG2-1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
ZDHHC3ENST00000424952.7 linkc.287G>A p.Arg96Gln missense_variant 2/71 NM_001135179.2 ENSP00000395502.2 Q9NYG2-1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD3 exomes
AF:
0.00000796
AC:
2
AN:
251282
Hom.:
0
AF XY:
0.0000147
AC XY:
2
AN XY:
135840
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000176
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000116
AC:
17
AN:
1461872
Hom.:
0
Cov.:
31
AF XY:
0.0000138
AC XY:
10
AN XY:
727238
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:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000153
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32
Bravo
AF:
0.00000378
ExAC
AF:
0.0000165
AC:
2

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 submitterclinical testingAmbry GeneticsJan 09, 2023The c.287G>A (p.R96Q) alteration is located in exon 2 (coding exon 1) of the ZDHHC3 gene. This alteration results from a G to A substitution at nucleotide position 287, causing the arginine (R) at amino acid position 96 to be replaced by a glutamine (Q). 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
0.30
BayesDel_addAF
Benign
-0.055
T
BayesDel_noAF
Benign
-0.25
CADD
Pathogenic
33
DANN
Pathogenic
1.0
DEOGEN2
Benign
0.16
.;T;.
Eigen
Uncertain
0.24
Eigen_PC
Benign
0.21
FATHMM_MKL
Uncertain
0.91
D
M_CAP
Benign
0.037
D
MetaRNN
Uncertain
0.45
T;T;T
MetaSVM
Benign
-0.71
T
MutationAssessor
Uncertain
2.3
M;M;.
PrimateAI
Uncertain
0.62
T
PROVEAN
Uncertain
-2.8
D;D;D
REVEL
Benign
0.17
Sift
Uncertain
0.0060
D;D;D
Sift4G
Uncertain
0.030
D;D;D
Polyphen
1.0
D;D;.
Vest4
0.59
MutPred
0.52
Loss of methylation at R96 (P = 0.0223);Loss of methylation at R96 (P = 0.0223);Loss of methylation at R96 (P = 0.0223);
MVP
0.42
MPC
1.2
ClinPred
0.89
D
GERP RS
2.6
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
Varity_R
0.29
gMVP
0.94

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs753044925; hg19: chr3-45000642; API