11-19152615-G-A

Position:

• chr11-19152615-G-A

Variant summary

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

The ENST00000446113.7(ZDHHC13):​c.804G>A​(p.Met268Ile) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/21 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: ZDHHC13 ENST00000446113.7 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.86

Genes affected

ZDHHC13 (HGNC:18413): (zinc finger DHHC-type palmitoyltransferase 13) Predicted to enable magnesium ion transmembrane transporter activity and palmitoyltransferase activity. Involved in positive regulation of I-kappaB kinase/NF-kappaB signaling. Located in endoplasmic reticulum. [provided by Alliance of Genome Resources, Apr 2022]

ZDHHC13 (HGNC:):

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=0.16051713).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZDHHC13	NM_019028.3	c.804G>A	p.Met268Ile	missense_variant	8/17	ENST00000446113.7	NP_061901.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZDHHC13	ENST00000446113.7	c.804G>A	p.Met268Ile	missense_variant	8/17	1	NM_019028.3	ENSP00000400113.2
ZDHHC13	ENST00000399351.7	c.414G>A	p.Met138Ile	missense_variant	7/16	1		ENSP00000382288.3

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

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Apr 11, 2023

The c.804G>A (p.M268I) alteration is located in exon 8 (coding exon 8) of the ZDHHC13 gene. This alteration results from a G to A substitution at nucleotide position 804, causing the methionine (M) at amino acid position 268 to be replaced by an isoleucine (I). 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	0.35
BayesDel_addAF	Benign	-0.12	T
BayesDel_noAF	Benign	-0.41
CADD	Benign	23
DANN	Benign	0.97
DEOGEN2	Benign	0.062	T;.
Eigen	Benign	-0.16
Eigen_PC	Benign	0.090
FATHMM_MKL	Uncertain	0.84	D
LIST_S2	Benign	0.71	T;T
M_CAP	Benign	0.0098	T
MetaRNN	Benign	0.16	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-0.50	N;.
MutationTaster	Benign	1.0	D;D
PrimateAI	Uncertain	0.54	T
PROVEAN	Benign	-1.4	N;N
REVEL	Benign	0.059
Sift	Benign	0.43	T;T
Sift4G	Benign	0.47	T;T
Polyphen		0.0080	B;.
Vest4		0.36
MutPred		0.51		Gain of catalytic residue at Q263 (P = 0.0874);.;
MVP		0.47
MPC		0.038
ClinPred		0.66	D
GERP RS		5.5
Varity_R		0.14
gMVP		0.58

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

Other links and lift over

dbSNP: rs1849644548; hg19: chr11-19174162;