11-57695957-C-T

Variant names:

• chr11-57695957-C-T
• NM_015457.3:c.923C>T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_015457.3(ZDHHC5):​c.923C>T​(p.Ala308Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. 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: 3.52

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.13395724).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZDHHC5	NM_015457.3	c.923C>T	p.Ala308Val	missense_variant	Exon 9 of 12	ENST00000287169.8	NP_056272.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZDHHC5	ENST00000287169.8	c.923C>T	p.Ala308Val	missense_variant	Exon 9 of 12	1	NM_015457.3	ENSP00000287169.3
ZDHHC5	ENST00000527985.5	c.764C>T	p.Ala255Val	missense_variant	Exon 8 of 11	1		ENSP00000432202.1
ZDHHC5	ENST00000529480.1	n.1170C>T		non_coding_transcript_exon_variant	Exon 7 of 10	1
ZDHHC5	ENST00000529447.1	c.425C>T	p.Ala142Val	missense_variant	Exon 5 of 7	5		ENSP00000435722.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Sep 22, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.923C>T (p.A308V) alteration is located in exon 9 (coding exon 8) of the ZDHHC5 gene. This alteration results from a C to T substitution at nucleotide position 923, causing the alanine (A) at amino acid position 308 to be replaced by a valine (V). 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	0.18
BayesDel_addAF	Benign	0.011	T
BayesDel_noAF	Benign	-0.22
CADD	Benign	22
DANN	Benign	0.43
DEOGEN2	Benign	0.060	.;T;T
Eigen	Benign	0.00052
Eigen_PC	Benign	0.16
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Uncertain	0.90	D;D;D
M_CAP	Benign	0.025	D
MetaRNN	Benign	0.13	T;T;T
MetaSVM	Benign	-0.37	T
MutationAssessor	Benign	1.6	.;L;.
PrimateAI	Uncertain	0.74	T
PROVEAN	Benign	-0.96	N;N;N
REVEL	Benign	0.11
Sift	Benign	1.0	T;T;T
Sift4G	Benign	1.0	T;T;T
Polyphen		0.14	.;B;.
Vest4		0.15
MutPred		0.057		.;Loss of phosphorylation at T303 (P = 0.1685);.;
MVP		0.10
MPC		0.25
ClinPred		0.71	D
GERP RS		4.7
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.13
gMVP		0.38

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: chr11-57463429; COSMIC: COSV54708602; COSMIC: COSV54708602;