Genetic Variant ZBTB10:p.Pro47Arg (chr8-80486950-C-G) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001105539.3(ZBTB10):c.140C>G(p.Pro47Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000147 in 1,362,274 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P47S) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000015 ( 0 hom. )

Consequence

ZBTB10
NM_001105539.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.455

Publications

3 publications found

Variant links:

Genes affected

ZBTB10 (HGNC:30953): (zinc finger and BTB domain containing 10) Predicted to enable RNA polymerase II transcription regulatory region sequence-specific DNA binding activity. Predicted to be involved in regulation of transcription by RNA polymerase II. Located in nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

ZBTB10 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.15108585).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001105539.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ZBTB10	NM_001105539.3	MANE Select	c.140C>G	p.Pro47Arg	missense	Exon 1 of 6	NP_001099009.1	Q96DT7-1
ZBTB10	NM_023929.5		c.140C>G	p.Pro47Arg	missense	Exon 1 of 7	NP_076418.3
ZBTB10	NM_001277145.2		c.96+1071C>G		intron	N/A	NP_001264074.1	Q96DT7-4

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ZBTB10	ENST00000455036.8	TSL:2 MANE Select	c.140C>G	p.Pro47Arg	missense	Exon 1 of 6	ENSP00000412036.3	Q96DT7-1
ZBTB10	ENST00000430430.5	TSL:5	c.140C>G	p.Pro47Arg	missense	Exon 2 of 7	ENSP00000387462.1	Q96DT7-1
ZBTB10	ENST00000961791.1		c.140C>G	p.Pro47Arg	missense	Exon 2 of 7	ENSP00000631850.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000957

AC:

AN:

104488

AF XY:

0.0000171

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 FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000272

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000147

AC:

AN:

1362274

Hom.:

Cov.:

AF XY:

0.00000298

AC XY:

AN XY:

671872

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

27836

American (AMR)

AF:

0.00

AC:

AN:

32926

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

24002

East Asian (EAS)

AF:

0.00

AC:

AN:

32258

South Asian (SAS)

AF:

0.00

AC:

AN:

76774

European-Finnish (FIN)

AF:

0.00

AC:

AN:

39398

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4482

European-Non Finnish (NFE)

AF:

0.00000187

AC:

AN:

1067970

Other (OTH)

AF:

0.00

AC:

AN:

56628

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome 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

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.14

BayesDel_addAF

Benign

-0.27

BayesDel_noAF

Benign

-0.56

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.0045

Eigen

Benign

-0.72

Eigen_PC

Benign

-0.68

FATHMM_MKL

Benign

0.30

LIST_S2

Benign

0.63

M_CAP

Pathogenic

0.56

MetaRNN

Benign

0.15

MetaSVM

Benign

-0.97

MutationAssessor

Benign

0.0

PhyloP100

0.46

PrimateAI

Pathogenic

0.83

PROVEAN

Benign

-0.34

REVEL

Benign

0.018

Sift

Pathogenic

0.0

Sift4G

Uncertain

0.046

Polyphen

0.062

Vest4

0.30

MutPred

0.21

Loss of glycosylation at P47 (P = 0.005)

MVP

0.043

MPC

0.75

ClinPred

0.22

GERP RS

-0.20

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.15

gMVP

0.15

Mutation Taster

=94/6

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over