11-57673119-A-C

Variant names:

• chr11-57673119-A-C
• NM_015457.3:c.29A>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
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.21

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]

ACMG classification

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
ZDHHC5	NM_015457.3	c.29A>C	p.Lys10Thr	missense_variant	Exon 2 of 12	ENST00000287169.8	NP_056272.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZDHHC5	ENST00000287169.8	c.29A>C	p.Lys10Thr	missense_variant	Exon 2 of 12	1	NM_015457.3	ENSP00000287169.3
ZDHHC5	ENST00000527985.5	c.-56+4932A>C		intron_variant	Intron 1 of 10	1		ENSP00000432202.1
ZDHHC5	ENST00000528177.5	c.-81+4932A>C		intron_variant	Intron 1 of 4	4		ENSP00000431209.1
ZDHHC5	ENST00000532842.1	c.-156A>C		upstream_gene_variant		5		ENSP00000435593.1

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

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;