Variant chr3-167282491-C-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_001199201.2(ZBBX):c.2001G>T(p.Gln667His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000257 in 1,597,828 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

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

Exomes 𝑓: 0.000027 ( 0 hom. )

Consequence

ZBBX
NM_001199201.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.08

Variant links:

Genes affected

ZBBX (HGNC:26245): (zinc finger B-box domain containing) Predicted to enable zinc ion binding activity. Predicted to be involved in cilium movement. Predicted to be active in motile cilium. [provided by Alliance of Genome Resources, Apr 2022]

ZBBX 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=0.1016818).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ZBBX	NM_001199201.2 linkuse as main transcript	c.2001G>T	p.Gln667His	missense_variant	20/22	ENST00000675490.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ZBBX	ENST00000675490.1 linkuse as main transcript	c.2001G>T	p.Gln667His	missense_variant	20/22		NM_001199201.2	P4	A8MT70-2

Frequencies

GnomAD3 genomes

AF:

0.0000131

AC:

AN:

152092

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

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:

0.0000128

AC:

AN:

234194

Hom.:

AF XY:

0.00000785

AC XY:

AN XY:

127448

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:

0.0000276

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000270

AC:

AN:

1445736

Hom.:

Cov.:

AF XY:

0.0000306

AC XY:

AN XY:

718686

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:

0.0000352

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000131

AC:

AN:

152092

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74276

show subpopulations

Gnomad4 AFR

AF:

0.0000241

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

Alfa

AF:

0.0000282

Hom.:

Bravo

AF:

0.0000264

ExAC

AF:

0.00000828

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

Oct 12, 2022

The c.2001G>T (p.Q667H) alteration is located in exon 20 (coding exon 17) of the ZBBX gene. This alteration results from a G to T substitution at nucleotide position 2001, causing the glutamine (Q) at amino acid position 667 to be replaced by a histidine (H). 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

0.23

BayesDel_addAF

Benign

-0.31

BayesDel_noAF

Benign

-0.62

CADD

Benign

DANN

Benign

0.78

DEOGEN2

Benign

0.010

T;.;.;.;.

Eigen

Benign

-0.62

Eigen_PC

Benign

-0.72

FATHMM_MKL

Benign

0.038

LIST_S2

Benign

0.37

T;T;T;.;.

M_CAP

Benign

0.0073

MetaRNN

Benign

0.083

T;T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Uncertain

2.3

M;.;.;.;.

MutationTaster

Benign

1.0

N;N;N;N;N

PrimateAI

Benign

0.25

PROVEAN

Benign

-2.2

N;.;N;N;N

REVEL

Benign

0.038

Sift

Uncertain

0.022

D;.;D;D;D

Sift4G

Uncertain

0.050

T;T;T;T;T

Polyphen

0.70

P;.;P;P;.

Vest4

0.11

MutPred

0.15

Gain of sheet (P = 0.0344);.;.;.;.;

MVP

0.055

MPC

0.086

ClinPred

0.39

GERP RS

1.8

Varity_R

0.072

gMVP

0.15

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