Genetic Variant ZBTB8OS:p.Val153Ile (chr1-32621909-C-T) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_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. 14/19 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

Publications

0 publications found

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 was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

BP4

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_178547.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ZBTB8OS	NM_178547.5	MANE Select	c.457G>A	p.Val153Ile	missense	Exon 7 of 7	NP_848642.2	Q8IWT0-1
ZBTB8OS	NM_001366264.1		c.529G>A	p.Val177Ile	missense	Exon 7 of 7	NP_001353193.1
ZBTB8OS	NM_001308135.2		c.472G>A	p.Val158Ile	missense	Exon 6 of 6	NP_001295064.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ZBTB8OS	ENST00000468695.6	TSL:1 MANE Select	c.457G>A	p.Val153Ile	missense	Exon 7 of 7	ENSP00000417677.2	Q8IWT0-1
ZBTB8OS	ENST00000436661.6	TSL:1	c.404G>A	p.Gly135Asp	missense	Exon 6 of 6	ENSP00000413485.2	Q8IWT0-2
ZBTB8OS	ENST00000341885.6	TSL:1	c.98-21559G>A		intron	N/A	ENSP00000343760.6	F6SII6

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

GnomAD2 exomes

AF:

0.0000171

AC:

AN:

234142

AF XY:

0.0000158

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 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

African (AFR)

AF:

0.000279

AC:

AN:

32250

American (AMR)

AF:

0.00

AC:

AN:

39416

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25820

East Asian (EAS)

AF:

0.00

AC:

AN:

39346

South Asian (SAS)

AF:

0.00

AC:

AN:

80606

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52432

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4508

European-Non Finnish (NFE)

AF:

0.00000541

AC:

AN:

1108308

Other (OTH)

AF:

0.0000336

AC:

AN:

59580

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.452

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.000107

AC:

AN:

150222

Hom.:

Cov.:

AF XY:

0.000109

AC XY:

AN XY:

73128

show subpopulations

African (AFR)

AF:

0.000369

AC:

AN:

40698

American (AMR)

AF:

0.00

AC:

AN:

15070

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5176

South Asian (SAS)

AF:

0.00

AC:

AN:

4792

European-Finnish (FIN)

AF:

0.00

AC:

AN:

9894

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.0000147

AC:

AN:

67830

Other (OTH)

AF:

0.00

AC:

AN:

2064

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.531

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.0000756

ExAC

AF:

0.0000165

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.087

BayesDel_addAF

Benign

-0.39

BayesDel_noAF

Benign

-0.50

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.025

Eigen

Benign

-0.60

Eigen_PC

Benign

-0.36

FATHMM_MKL

Benign

0.56

LIST_S2

Uncertain

0.91

M_CAP

Benign

0.0027

MetaRNN

Benign

0.034

MetaSVM

Benign

-0.98

PhyloP100

1.7

PrimateAI

Benign

0.45

PROVEAN

Benign

0.33

REVEL

Benign

0.036

Sift

Benign

1.0

Sift4G

Benign

1.0

Polyphen

0.011

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

Mutation Taster

=88/12

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over