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GeneBe

13-21376655-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The ENST00000382466.7(ZDHHC20):c.1058G>A(p.Gly353Asp) variant causes a missense, splice region change. The variant allele was found at a frequency of 0.0000376 in 1,409,792 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/19 in silico tools predict a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000026 ( 0 hom., cov: 33)
Exomes 𝑓: 0.000039 ( 0 hom. )

Consequence

ZDHHC20
ENST00000382466.7 missense, splice_region

Scores

5
11
Splicing: ADA: 0.7359
2

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.35
Variant links:
Genes affected
ZDHHC20 (HGNC:20749): (zinc finger DHHC-type palmitoyltransferase 20) Enables protein-cysteine S-palmitoyltransferase activity and zinc ion binding activity. Involved in peptidyl-L-cysteine S-palmitoylation. Located in intracellular membrane-bounded organelle and plasma membrane. Is integral component of Golgi membrane. [provided by Alliance of Genome Resources, Apr 2022]

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.30644625).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
ZDHHC20NM_001330059.2 linkuse as main transcriptc.*41G>A splice_region_variant, 3_prime_UTR_variant 13/13 ENST00000400590.8
MIPEPP3NR_046461.1 linkuse as main transcriptn.571-15095C>T intron_variant, non_coding_transcript_variant
LOC124903130XM_047430813.1 linkuse as main transcript upstream_gene_variant

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
ZDHHC20ENST00000400590.8 linkuse as main transcriptc.*41G>A splice_region_variant, 3_prime_UTR_variant 13/135 NM_001330059.2 P1Q5W0Z9-1

Frequencies

GnomAD3 genomes
AF:
0.0000263
AC:
4
AN:
152034
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000588
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000183
AC:
2
AN:
109350
Hom.:
0
AF XY:
0.0000342
AC XY:
2
AN XY:
58430
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:
0.0000432
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000390
AC:
49
AN:
1257642
Hom.:
0
Cov.:
20
AF XY:
0.0000322
AC XY:
20
AN XY:
621554
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:
0.0000458
Gnomad4 OTH exome
AF:
0.0000767
GnomAD4 genome
AF:
0.0000263
AC:
4
AN:
152150
Hom.:
0
Cov.:
33
AF XY:
0.0000269
AC XY:
2
AN XY:
74374
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000588
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000387
Hom.:
0
Bravo
AF:
0.0000189

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 GeneticsJun 13, 2023The c.1058G>A (p.G353D) alteration is located in exon 12 (coding exon 12) of the ZDHHC20 gene. This alteration results from a G to A substitution at nucleotide position 1058, causing the glycine (G) at amino acid position 353 to be replaced by an aspartic acid (D). 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
BayesDel_addAF
Benign
-0.027
T
BayesDel_noAF
Benign
-0.15
Cadd
Benign
19
Dann
Uncertain
0.99
Eigen
Benign
-0.022
Eigen_PC
Benign
0.12
FATHMM_MKL
Uncertain
0.87
D
LIST_S2
Benign
0.42
T;T
M_CAP
Benign
0.020
T
MetaRNN
Benign
0.31
T;T
MetaSVM
Benign
-1.0
T
MutationTaster
Benign
1.0
D;D;D;D
PrimateAI
Uncertain
0.50
T
PROVEAN
Benign
-1.5
N;N
REVEL
Benign
0.12
Sift
Uncertain
0.0060
D;D
Sift4G
Uncertain
0.045
D;D
Polyphen
0.025
B;B
Vest4
0.61
MVP
0.52
MPC
1.7
ClinPred
0.91
D
GERP RS
5.3

Splicing

Name
Calibrated prediction
Score
Prediction
dbscSNV1_ADA
Benign
0.74
dbscSNV1_RF
Benign
0.51
SpliceAI score (max)
0.17
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: rs1276415331; hg19: chr13-21950794; API