Variant 12-107319653-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_001018072.2(ABTB3):c.713C>T(p.Thr238Ile) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

ABTB3
NM_001018072.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.62

Variant links:

Genes affected

ABTB3 (HGNC:23844): (ankyrin repeat and BTB domain containing 3) Predicted to enable protein heterodimerization activity. Predicted to be involved in SMAD protein signal transduction. Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

ABTB3 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=0.19056624).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
ABTB3	NM_001018072.2 linkuse as main transcript	c.713C>T	p.Thr238Ile	missense_variant	1/17	ENST00000280758.10
ABTB3	NM_001347943.2 linkuse as main transcript	c.713C>T	p.Thr238Ile	missense_variant	1/15
ABTB3	XM_047428301.1 linkuse as main transcript	c.713C>T	p.Thr238Ile	missense_variant	1/16

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	UniProt
ABTB3	ENST00000280758.10 linkuse as main transcript	c.713C>T	p.Thr238Ile	missense_variant	1/17	5	NM_001018072.2	A6QL63-1
ABTB3	ENST00000490090.6 linkuse as main transcript	c.713C>T	p.Thr238Ile	missense_variant	1/15	2		A6QL63-3
ABTB3	ENST00000420571.6 linkuse as main transcript	c.713C>T	p.Thr238Ile	missense_variant	1/15	5		A6QL63-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1385062

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

683746

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

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:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

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 14, 2023

The c.713C>T (p.T238I) alteration is located in exon 1 (coding exon 1) of the BTBD11 gene. This alteration results from a C to T substitution at nucleotide position 713, causing the threonine (T) at amino acid position 238 to be replaced by an isoleucine (I). 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

Pathogenic

0.85

BayesDel_addAF

Benign

-0.13

BayesDel_noAF

Benign

-0.42

CADD

Pathogenic

DANN

Uncertain

0.99

DEOGEN2

Benign

0.21

T;.;.

Eigen

Benign

0.055

Eigen_PC

Benign

0.17

FATHMM_MKL

Uncertain

0.85

LIST_S2

Benign

0.82

T;T;T

M_CAP

Benign

0.018

MetaRNN

Benign

0.19

T;T;T

MetaSVM

Benign

-0.87

MutationAssessor

Uncertain

2.1

M;M;M

MutationTaster

Benign

0.98

D;D;D

PrimateAI

Pathogenic

0.82

PROVEAN

Uncertain

-2.8

D;D;D

REVEL

Benign

0.087

Sift

Uncertain

0.0060

D;D;D

Sift4G

Uncertain

0.033

D;D;D

Polyphen

0.0050

B;B;B

Vest4

0.44

MutPred

0.43

Gain of catalytic residue at I235 (P = 2e-04);Gain of catalytic residue at I235 (P = 2e-04);Gain of catalytic residue at I235 (P = 2e-04);

MVP

0.21

MPC

1.1

ClinPred

0.96

GERP RS

3.8

Varity_R

0.20

gMVP

0.68

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

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over