Variant 1-32633978-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_178547.5(ZBTB8OS):c.217C>T(p.Leu73Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000283 in 1,588,090 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 11/17 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00016 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000015 ( 0 hom. )

Consequence

ZBTB8OS
NM_178547.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.15

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:

ZBTB8OS (HGNC:):

ZBTB8OS 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=0.0872865).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZBTB8OS	NM_178547.5 linkuse as main transcript	c.217C>T	p.Leu73Phe	missense_variant	3/7	ENST00000468695.6	NP_848642.2	Q8IWT0-1A8K0B5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZBTB8OS	ENST00000468695.6 linkuse as main transcript	c.217C>T	p.Leu73Phe	missense_variant	3/7	1	NM_178547.5	ENSP00000417677.2		Q8IWT0-1A8K0B5

Frequencies

GnomAD3 genomes

AF:

0.000158

AC:

AN:

152100

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000531

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000399

AC:

AN:

225484

Hom.:

AF XY:

0.0000164

AC XY:

AN XY:

122140

show subpopulations

Gnomad AFR exome

AF:

0.000507

Gnomad AMR exome

AF:

0.0000377

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:

0.0000146

AC:

AN:

1435990

Hom.:

Cov.:

AF XY:

0.0000154

AC XY:

AN XY:

714176

show subpopulations

Gnomad4 AFR exome

AF:

0.000504

Gnomad4 AMR exome

AF:

0.0000836

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:

9.05e-7

Gnomad4 OTH exome

AF:

0.0000169

GnomAD4 genome

AF:

0.000158

AC:

AN:

152100

Hom.:

Cov.:

AF XY:

0.000175

AC XY:

AN XY:

74298

show subpopulations

Gnomad4 AFR

AF:

0.000531

Gnomad4 AMR

AF:

0.000131

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000298

Hom.:

Bravo

AF:

0.000117

ESP6500AA

AF:

0.00136

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.0000494

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

Mar 16, 2022

The c.253C>T (p.L85F) alteration is located in exon 3 (coding exon 3) of the ZBTB8OS gene. This alteration results from a C to T substitution at nucleotide position 253, causing the leucine (L) at amino acid position 85 to be replaced by a phenylalanine (F). 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

-0.37

BayesDel_noAF

Benign

-0.43

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.029

T;.;T

Eigen

Benign

0.10

Eigen_PC

Benign

0.13

FATHMM_MKL

Benign

0.68

LIST_S2

Uncertain

0.95

D;.;D

M_CAP

Benign

0.0046

MetaRNN

Benign

0.087

T;T;T

MetaSVM

Benign

-0.80

PrimateAI

Benign

0.46

PROVEAN

Benign

-1.6

N;.;.

REVEL

Benign

0.16

Sift

Benign

0.049

D;.;.

Sift4G

Uncertain

0.049

D;D;D

Polyphen

0.97

D;.;.

Vest4

0.25

MVP

0.34

MPC

0.85

ClinPred

0.080

GERP RS

3.5

gMVP

0.40

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