Variant 11-19149302-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_019028.3(ZDHHC13):c.490A>G(p.Ile164Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000187 in 1,602,656 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000066 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000014 ( 0 hom. )

Consequence

ZDHHC13
NM_019028.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.55

Variant links:

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 links:

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ACMG classification

Classification made for transcript

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=0.122428834).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZDHHC13	NM_019028.3 linkuse as main transcript	c.490A>G	p.Ile164Val	missense_variant	5/17	ENST00000446113.7	NP_061901.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZDHHC13	ENST00000446113.7 linkuse as main transcript	c.490A>G	p.Ile164Val	missense_variant	5/17	1	NM_019028.3	ENSP00000400113	P1	Q8IUH4-1

Frequencies

GnomAD3 genomes

AF:

0.0000657

AC:

AN:

152218

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000589

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00000428

AC:

AN:

233560

Hom.:

AF XY:

0.00

AC XY:

AN XY:

126342

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:

0.00000955

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000138

AC:

AN:

1450438

Hom.:

Cov.:

AF XY:

0.00000833

AC XY:

AN XY:

720402

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000229

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:

0.0000145

Gnomad4 OTH exome

AF:

0.0000501

GnomAD4 genome

AF:

0.0000657

AC:

AN:

152218

Hom.:

Cov.:

AF XY:

0.0000672

AC XY:

AN XY:

74364

show subpopulations

Gnomad4 AFR

AF:

0.0000241

Gnomad4 AMR

AF:

0.000589

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000434

Hom.:

Bravo

AF:

0.0000945

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 submitter

clinical testing

Ambry Genetics

Oct 04, 2022

The c.490A>G (p.I164V) alteration is located in exon 5 (coding exon 5) of the ZDHHC13 gene. This alteration results from a A to G substitution at nucleotide position 490, causing the isoleucine (I) at amino acid position 164 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

0.068

BayesDel_addAF

Benign

-0.10

BayesDel_noAF

Benign

-0.39

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.043

T;.

Eigen

Benign

-0.20

Eigen_PC

Benign

0.029

FATHMM_MKL

Uncertain

0.93

LIST_S2

Benign

0.76

T;T

M_CAP

Benign

0.017

MetaRNN

Benign

0.12

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.045

N;.

MutationTaster

Benign

1.0

D;D

PrimateAI

Benign

0.35

PROVEAN

Benign

-0.71

N;N

REVEL

Benign

0.078

Sift

Benign

0.054

T;D

Sift4G

Benign

0.16

T;T

Polyphen

0.0080

B;.

Vest4

0.19

MutPred

0.52

Gain of catalytic residue at I164 (P = 0.0649);.;

MVP

0.37

MPC

0.032

ClinPred

0.30

GERP RS

4.7

Varity_R

0.073

gMVP

0.27

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over