Variant 11-19152682-G-A 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.871G>A(p.Glu291Lys) variant causes a missense, splice region change. The variant allele was found at a frequency of 0.00000992 in 1,612,896 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/23 in silico tools predict a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000096 ( 0 hom. )

Consequence

ZDHHC13
NM_019028.3 missense, splice_region

Scores

Splicing: ADA: 0.001007

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.25

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:

Genome browser will be placed here

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=0.1644713).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZDHHC13	NM_019028.3 linkuse as main transcript	c.871G>A	p.Glu291Lys	missense_variant, splice_region_variant	8/17	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.871G>A	p.Glu291Lys	missense_variant, splice_region_variant	8/17	1	NM_019028.3	ENSP00000400113	P1	Q8IUH4-1
ZDHHC13	ENST00000399351.7 linkuse as main transcript	c.481G>A	p.Glu161Lys	missense_variant, splice_region_variant	7/16	1		ENSP00000382288		Q8IUH4-3
ZDHHC13	ENST00000525490.5 linkuse as main transcript	n.819G>A		splice_region_variant, non_coding_transcript_exon_variant	7/15	1
ZDHHC13	ENST00000532812.5 linkuse as main transcript	n.704G>A		splice_region_variant, non_coding_transcript_exon_variant	5/6	3

Frequencies

GnomAD3 genomes

AF:

0.0000131

AC:

AN:

152094

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000242

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000201

AC:

AN:

249008

Hom.:

AF XY:

0.0000148

AC XY:

AN XY:

135096

show subpopulations

Gnomad AFR exome

AF:

0.0000646

Gnomad AMR exome

AF:

0.0000290

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000327

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000177

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000958

AC:

AN:

1460802

Hom.:

Cov.:

AF XY:

0.00000826

AC XY:

AN XY:

726670

show subpopulations

Gnomad4 AFR exome

AF:

0.0000299

Gnomad4 AMR exome

AF:

0.0000224

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:

0.00000990

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

AF:

0.0000131

AC:

AN:

152094

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74302

show subpopulations

Gnomad4 AFR

AF:

0.0000242

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000151

ExAC

AF:

0.0000331

AC:

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

Apr 01, 2024

The c.871G>A (p.E291K) 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 871, causing the glutamic acid (E) at amino acid position 291 to be replaced by a lysine (K). 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

0.25

BayesDel_addAF

Benign

-0.086

BayesDel_noAF

Benign

-0.18

CADD

Benign

DANN

Benign

0.66

DEOGEN2

Benign

0.041

T;.

Eigen

Benign

-0.11

Eigen_PC

Benign

0.093

FATHMM_MKL

Pathogenic

0.97

LIST_S2

Benign

0.85

T;T

M_CAP

Benign

0.0074

MetaRNN

Benign

0.16

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.8

L;.

MutationTaster

Benign

1.0

D;D

PrimateAI

Uncertain

0.56

PROVEAN

Benign

0.45

N;N

REVEL

Benign

0.15

Sift

Benign

1.0

T;T

Sift4G

Benign

1.0

T;T

Polyphen

0.021

B;.

Vest4

0.37

MutPred

0.54

Gain of MoRF binding (P = 0.0053);.;

MVP

0.58

MPC

0.038

ClinPred

0.12

GERP RS

5.4

Varity_R

0.13

gMVP

0.63

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.0010

dbscSNV1_RF

Benign

0.028

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