Variant 20-57611885-G-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 NM_030776.3(ZBP1):c.716C>A(p.Ser239Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000352 in 1,422,118 control chromosomes in the GnomAD database, with no homozygous occurrence. 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)

Exomes 𝑓: 0.0000035 ( 0 hom. )

Consequence

ZBP1
NM_030776.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.624

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:

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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=0.15477759).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ZBP1	NM_030776.3 linkuse as main transcript	c.716C>A	p.Ser239Tyr	missense_variant	6/8	ENST00000371173.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ZBP1	ENST00000371173.8 linkuse as main transcript	c.716C>A	p.Ser239Tyr	missense_variant	6/8	1	NM_030776.3	P2	Q9H171-1
ZBP1	ENST00000395822.7 linkuse as main transcript	c.491C>A	p.Ser164Tyr	missense_variant	5/7	2			Q9H171-7
ZBP1	ENST00000461547.5 linkuse as main transcript	n.2958C>A		non_coding_transcript_exon_variant	4/7	2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000352

AC:

AN:

1422118

Hom.:

Cov.:

AF XY:

0.00000426

AC XY:

AN XY:

703592

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000367

Gnomad4 OTH exome

AF:

0.0000170

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000386

Hom.:

Bravo

AF:

0.0000113

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

Jan 07, 2022

The c.716C>A (p.S239Y) alteration is located in exon 6 (coding exon 6) of the ZBP1 gene. This alteration results from a C to A substitution at nucleotide position 716, causing the serine (S) at amino acid position 239 to be replaced by a tyrosine (Y). 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

0.13

BayesDel_addAF

Benign

-0.30

BayesDel_noAF

Benign

-0.66

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.021

T;.

Eigen

Benign

-0.43

Eigen_PC

Benign

-0.65

FATHMM_MKL

Benign

0.069

LIST_S2

Benign

0.59

T;T

M_CAP

Benign

0.0027

MetaRNN

Benign

0.15

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

2.0

M;.

MutationTaster

Benign

1.0

N;N;N;N

PrimateAI

Benign

0.30

PROVEAN

Uncertain

-3.3

D;D

REVEL

Benign

0.019

Sift

Uncertain

0.022

D;D

Sift4G

Uncertain

0.034

D;D

Polyphen

0.98

D;.

Vest4

0.22

MutPred

0.20

Loss of disorder (P = 0.003);.;

MVP

0.25

MPC

0.28

ClinPred

0.56

GERP RS

1.1

Varity_R

0.078

gMVP

0.088

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.18

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