Genetic Variant ZBTB10:p.Ala37Ser (chr8-80486919-G-T) – 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.109G>T(p.Ala37Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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. A37P) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

ZBTB10
NM_001105539.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.00500

Publications

1 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:

ENSG00000251867 (HGNC:):

ENSG00000251867 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=0.11722052).

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.109G>T	p.Ala37Ser	missense	Exon 1 of 6	NP_001099009.1	Q96DT7-1
ZBTB10	NM_023929.5		c.109G>T	p.Ala37Ser	missense	Exon 1 of 7	NP_076418.3
ZBTB10	NM_001277145.2		c.96+1040G>T		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.109G>T	p.Ala37Ser	missense	Exon 1 of 6	ENSP00000412036.3	Q96DT7-1
ZBTB10	ENST00000430430.5	TSL:5	c.109G>T	p.Ala37Ser	missense	Exon 2 of 7	ENSP00000387462.1	Q96DT7-1
ZBTB10	ENST00000961791.1		c.109G>T	p.Ala37Ser	missense	Exon 2 of 7	ENSP00000631850.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1357546

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

669114

African (AFR)

AF:

0.00

AC:

AN:

27654

American (AMR)

AF:

0.00

AC:

AN:

32692

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

23716

East Asian (EAS)

AF:

0.00

AC:

AN:

31576

South Asian (SAS)

AF:

0.00

AC:

AN:

75904

European-Finnish (FIN)

AF:

0.00

AC:

AN:

40326

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4038

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1065230

Other (OTH)

AF:

0.00

AC:

AN:

56410

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.072

BayesDel_addAF

Benign

-0.35

BayesDel_noAF

Benign

-0.74

CADD

Benign

8.9

(source)

DANN

Uncertain

0.98

DEOGEN2

Benign

0.0048

Eigen

Benign

-0.88

Eigen_PC

Benign

-0.80

FATHMM_MKL

Benign

0.37

LIST_S2

Benign

0.45

M_CAP

Pathogenic

0.35

MetaRNN

Benign

0.12

MetaSVM

Benign

-0.95

MutationAssessor

Benign

0.0

PhyloP100

-0.0050

PrimateAI

Pathogenic

0.85

PROVEAN

Benign

-0.16

REVEL

Benign

0.043

Sift

Benign

0.21

Sift4G

Benign

0.45

Polyphen

0.0

Vest4

0.11

MutPred

0.094

Gain of phosphorylation at A37 (P = 0.018)

MVP

0.043

MPC

0.62

ClinPred

0.051

GERP RS

-0.16

Varity_R

0.049

gMVP

0.062

Mutation Taster

=97/3

polymorphism

(source)

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

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over