Variant 8-80486926-C-T 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_001105539.3(ZBTB10):c.116C>T(p.Pro39Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000192 in 1,507,660 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.000026 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000018 ( 0 hom. )

Consequence

ZBTB10
NM_001105539.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.187

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:

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=0.09013006).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZBTB10	NM_001105539.3 linkuse as main transcript	c.116C>T	p.Pro39Leu	missense_variant	1/6	ENST00000455036.8	NP_001099009.1	Q96DT7-1
ZBTB10	NM_023929.5 linkuse as main transcript	c.116C>T	p.Pro39Leu	missense_variant	1/7		NP_076418.3	Q96DT7-2Q9H9H3
ZBTB10	NM_001277145.2 linkuse as main transcript	c.96+1047C>T		intron_variant			NP_001264074.1	Q96DT7-4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
ZBTB10	ENST00000455036.8 linkuse as main transcript	c.116C>T	p.Pro39Leu	missense_variant	1/6	2	NM_001105539.3	ENSP00000412036.3	Q96DT7-1
ZBTB10	ENST00000430430.5 linkuse as main transcript	c.116C>T	p.Pro39Leu	missense_variant	2/7	5		ENSP00000387462.1	Q96DT7-1
ZBTB10	ENST00000426744.5 linkuse as main transcript	c.116C>T	p.Pro39Leu	missense_variant	1/7	5		ENSP00000416134.2	Q96DT7-2
ZBTB10	ENST00000379091.8 linkuse as main transcript	c.96+1047C>T		intron_variant		2		ENSP00000368384.4	Q96DT7-4

Frequencies

GnomAD3 genomes

AF:

0.0000264

AC:

AN:

151410

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

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:

0.0000296

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000205

AC:

AN:

97644

Hom.:

AF XY:

0.0000366

AC XY:

AN XY:

54632

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 SAS exome

AF:

0.0000530

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.000334

GnomAD4 exome

AF:

0.0000184

AC:

AN:

1356250

Hom.:

Cov.:

AF XY:

0.0000180

AC XY:

AN XY:

668354

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000920

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000317

Gnomad4 SAS exome

AF:

0.0000132

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000150

Gnomad4 OTH exome

AF:

0.0000355

GnomAD4 genome

AF:

0.0000264

AC:

AN:

151410

Hom.:

Cov.:

AF XY:

0.0000271

AC XY:

AN XY:

73898

show subpopulations

Gnomad4 AFR

AF:

0.00

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:

0.0000296

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000227

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

Jul 05, 2024

The c.116C>T (p.P39L) alteration is located in exon 1 (coding exon 1) of the ZBTB10 gene. This alteration results from a C to T substitution at nucleotide position 116, causing the proline (P) at amino acid position 39 to be replaced by a leucine (L). 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

AlphaMissense

Benign

0.15

BayesDel_addAF

Benign

-0.43

BayesDel_noAF

Benign

-0.70

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.0051

T;T;.

Eigen

Benign

-0.57

Eigen_PC

Benign

-0.49

FATHMM_MKL

Benign

0.39

LIST_S2

Benign

0.77

.;T;T

M_CAP

Pathogenic

0.53

MetaRNN

Benign

0.090

T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.0

N;N;N

PrimateAI

Pathogenic

0.87

PROVEAN

Benign

-0.53

N;N;N

REVEL

Benign

0.058

Sift

Pathogenic

0.0

D;D;D

Sift4G

Uncertain

0.060

T;T;T

Polyphen

0.0010

B;B;B

Vest4

0.13

MutPred

0.14

Loss of glycosylation at P39 (P = 0.0073);Loss of glycosylation at P39 (P = 0.0073);Loss of glycosylation at P39 (P = 0.0073);

MVP

0.043

MPC

0.76

ClinPred

0.17

GERP RS

2.2

Varity_R

0.14

gMVP

0.16

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