Variant 1-32621909-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_178547.5(ZBTB8OS):c.457G>A(p.Val153Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000207 in 1,592,488 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/17 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00011 ( 0 hom., cov: 31)

Exomes 𝑓: 0.000012 ( 1 hom. )

Consequence

ZBTB8OS
NM_178547.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.69

Variant links:

Genes affected

ZBTB8OS (HGNC:24094): (zinc finger and BTB domain containing 8 opposite strand) Predicted to enable metal ion binding activity. Involved in tRNA splicing, via endonucleolytic cleavage and ligation. Part of tRNA-splicing ligase complex. [provided by Alliance of Genome Resources, Apr 2022]

ZBTB8OS links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.034125388).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ZBTB8OS	NM_178547.5 linkuse as main transcript	c.457G>A	p.Val153Ile	missense_variant	7/7	ENST00000468695.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ZBTB8OS	ENST00000468695.6 linkuse as main transcript	c.457G>A	p.Val153Ile	missense_variant	7/7	1	NM_178547.5	P1	Q8IWT0-1

Frequencies

GnomAD3 genomes

AF:

0.000107

AC:

AN:

150222

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000369

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:

0.0000171

AC:

AN:

234142

Hom.:

AF XY:

0.0000158

AC XY:

AN XY:

126728

show subpopulations

Gnomad AFR exome

AF:

0.000252

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:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000118

AC:

AN:

1442266

Hom.:

Cov.:

AF XY:

0.0000126

AC XY:

AN XY:

716918

show subpopulations

Gnomad4 AFR exome

AF:

0.000279

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:

0.00000541

Gnomad4 OTH exome

AF:

0.0000336

GnomAD4 genome

AF:

0.000107

AC:

AN:

150222

Hom.:

Cov.:

AF XY:

0.000109

AC XY:

AN XY:

73128

show subpopulations

Gnomad4 AFR

AF:

0.000369

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:

0.0000756

ExAC

AF:

0.0000165

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

Jan 30, 2024

The c.493G>A (p.V165I) alteration is located in exon 7 (coding exon 7) of the ZBTB8OS gene. This alteration results from a G to A substitution at nucleotide position 493, causing the valine (V) at amino acid position 165 to be replaced by an isoleucine (I). 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

BayesDel_addAF

Benign

-0.39

BayesDel_noAF

Benign

-0.50

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.025

T;.;T

Eigen

Benign

-0.60

Eigen_PC

Benign

-0.36

FATHMM_MKL

Benign

0.56

LIST_S2

Uncertain

0.91

D;.;D

M_CAP

Benign

0.0027

MetaRNN

Benign

0.034

T;T;T

MetaSVM

Benign

-0.98

MutationTaster

Benign

1.0

D;N;N

PrimateAI

Benign

0.45

PROVEAN

Benign

0.33

N;N;.

REVEL

Benign

0.036

Sift

Benign

1.0

T;T;.

Sift4G

Benign

1.0

T;T;T

Polyphen

0.011

B;.;.

Vest4

0.052

MutPred

0.69

Loss of phosphorylation at Y166 (P = 0.1138);.;.;

MVP

0.093

MPC

0.21

ClinPred

0.032

GERP RS

3.5

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

gMVP

0.15

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