11-57673119-A-C

Variant summary

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

The NM_015457.3(ZDHHC5):​c.29A>C​(p.Lys10Thr) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Consequence

ZDHHC5
NM_015457.3 missense

Scores

3
9
7

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.21
Variant links:
Genes affected
ZDHHC5 (HGNC:18472): (zinc finger DHHC-type palmitoyltransferase 5) Enables palmitoyltransferase activity. Involved in positive regulation of pattern recognition receptor signaling pathway and positive regulation of protein localization to plasma membrane. Acts upstream of or within protein palmitoylation. Located in phagocytic vesicle and plasma 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 2 ACMG points.

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

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
ZDHHC5NM_015457.3 linkc.29A>C p.Lys10Thr missense_variant Exon 2 of 12 ENST00000287169.8 NP_056272.2 Q9C0B5-1A0A024R546

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
ZDHHC5ENST00000287169.8 linkc.29A>C p.Lys10Thr missense_variant Exon 2 of 12 1 NM_015457.3 ENSP00000287169.3 Q9C0B5-1
ZDHHC5ENST00000527985.5 linkc.-56+4932A>C intron_variant Intron 1 of 10 1 ENSP00000432202.1 Q9C0B5-2
ZDHHC5ENST00000528177.5 linkc.-81+4932A>C intron_variant Intron 1 of 4 4 ENSP00000431209.1 E9PMA5
ZDHHC5ENST00000532842.1 linkc.-156A>C upstream_gene_variant 5 ENSP00000435593.1 E9PJ97

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Cov.:
30
GnomAD4 genome
Cov.:
32

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Mar 07, 2024
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.29A>C (p.K10T) alteration is located in exon 2 (coding exon 1) of the ZDHHC5 gene. This alteration results from a A to C substitution at nucleotide position 29, causing the lysine (K) at amino acid position 10 to be replaced by a threonine (T). 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
Uncertain
0.51
BayesDel_addAF
Uncertain
0.083
D
BayesDel_noAF
Benign
-0.12
CADD
Uncertain
25
DANN
Uncertain
1.0
DEOGEN2
Benign
0.045
T
Eigen
Uncertain
0.65
Eigen_PC
Pathogenic
0.68
FATHMM_MKL
Pathogenic
0.99
D
LIST_S2
Uncertain
0.88
D
M_CAP
Benign
0.019
T
MetaRNN
Uncertain
0.51
D
MetaSVM
Benign
-0.81
T
MutationAssessor
Benign
1.4
L
PrimateAI
Pathogenic
0.84
D
PROVEAN
Uncertain
-2.5
D
REVEL
Benign
0.25
Sift
Uncertain
0.0030
D
Sift4G
Uncertain
0.0090
D
Polyphen
1.0
D
Vest4
0.60
MutPred
0.43
Loss of methylation at K10 (P = 2e-04);
MVP
0.15
MPC
1.5
ClinPred
0.93
D
GERP RS
6.0
Varity_R
0.40
gMVP
0.69

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: chr11-57440591; API