Variant 20-57610254-C-T details in Genebe, Genetics Data Aggregator

Variant summary

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

The ENST00000371173.8(ZBP1):c.988G>A(p.Glu330Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000378 in 1,614,178 control chromosomes in the GnomAD database, including 1 homozygotes. 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: 𝑓 0.000039 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000038 ( 1 hom. )

Consequence

ZBP1
ENST00000371173.8 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.283

Variant links:

Genes affected

ZBP1 (HGNC:16176): (Z-DNA binding protein 1) This gene encodes a Z-DNA binding protein. The encoded protein plays a role in the innate immune response by binding to foreign DNA and inducing type-I interferon production. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, Dec 2011]

ZBP1 links:

ZBP1 (HGNC:):

ZBP1 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=0.09934771).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZBP1	NM_030776.3 linkuse as main transcript	c.988G>A	p.Glu330Lys	missense_variant	7/8	ENST00000371173.8	NP_110403.2	Q9H171-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
ZBP1	ENST00000371173.8 linkuse as main transcript	c.988G>A	p.Glu330Lys	missense_variant	7/8	1	NM_030776.3	ENSP00000360215.3	Q9H171-1
ZBP1	ENST00000395822.7 linkuse as main transcript	c.763G>A	p.Glu255Lys	missense_variant	6/7	2		ENSP00000379167.3	Q9H171-7
ZBP1	ENST00000453793.1 linkuse as main transcript	c.10G>A	p.Glu4Lys	missense_variant	1/2	3		ENSP00000404620.1	H0Y6D1
ZBP1	ENST00000461547.5 linkuse as main transcript	n.3393G>A		non_coding_transcript_exon_variant	6/7	2

Frequencies

GnomAD3 genomes

AF:

0.0000329

AC:

AN:

152176

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000961

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:

0.0000557

AC:

AN:

251482

Hom.:

AF XY:

0.0000589

AC XY:

AN XY:

135918

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000652

Gnomad SAS exome

AF:

0.0000327

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.000163

GnomAD4 exome

AF:

0.0000376

AC:

AN:

1461884

Hom.:

Cov.:

AF XY:

0.0000289

AC XY:

AN XY:

727246

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000277

Gnomad4 SAS exome

AF:

0.0000580

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000809

Gnomad4 OTH exome

AF:

0.000497

GnomAD4 genome

AF:

0.0000394

AC:

AN:

152294

Hom.:

Cov.:

AF XY:

0.0000403

AC XY:

AN XY:

74472

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000963

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.000474

Alfa

AF:

0.0000868

Hom.:

Bravo

AF:

0.0000529

ExAC

AF:

0.0000659

AC:

Asia WGS

AF:

0.00173

AC:

AN:

3478

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

Sep 07, 2022

The c.988G>A (p.E330K) alteration is located in exon 7 (coding exon 7) of the ZBP1 gene. This alteration results from a G to A substitution at nucleotide position 988, causing the glutamic acid (E) at amino acid position 330 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

0.15

BayesDel_addAF

Benign

-0.42

BayesDel_noAF

Benign

-0.51

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.054

T;.

Eigen

Benign

-0.051

Eigen_PC

Benign

-0.26

FATHMM_MKL

Benign

0.037

LIST_S2

Benign

0.72

T;T

M_CAP

Benign

0.0092

MetaRNN

Benign

0.099

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.4

L;.

MutationTaster

Benign

1.0

N;N;N;N

PrimateAI

Benign

0.39

PROVEAN

Uncertain

-2.5

D;D

REVEL

Benign

0.085

Sift

Uncertain

0.014

D;D

Sift4G

Pathogenic

0.0

D;D

Polyphen

1.0

D;.

Vest4

0.35

MutPred

0.40

Gain of MoRF binding (P = 0.0046);.;

MVP

0.32

MPC

0.049

ClinPred

0.21

GERP RS

3.1

Varity_R

0.13

gMVP

0.53

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

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