Variant 12-107319727-G-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.787G>T(p.Gly263Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000588 in 1,530,726 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000033 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0000029 ( 0 hom. )

Consequence

ABTB3
NM_001018072.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.20

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:

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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=0.098204195).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
ABTB3	NM_001018072.2 linkuse as main transcript	c.787G>T	p.Gly263Cys	missense_variant	1/17	ENST00000280758.10
ABTB3	NM_001347943.2 linkuse as main transcript	c.787G>T	p.Gly263Cys	missense_variant	1/15
ABTB3	XM_047428301.1 linkuse as main transcript	c.787G>T	p.Gly263Cys	missense_variant	1/16

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	UniProt
ABTB3	ENST00000280758.10 linkuse as main transcript	c.787G>T	p.Gly263Cys	missense_variant	1/17	5	NM_001018072.2	A6QL63-1
ABTB3	ENST00000490090.6 linkuse as main transcript	c.787G>T	p.Gly263Cys	missense_variant	1/15	2		A6QL63-3
ABTB3	ENST00000420571.6 linkuse as main transcript	c.787G>T	p.Gly263Cys	missense_variant	1/15	5		A6QL63-2

Frequencies

GnomAD3 genomes

AF:

0.0000330

AC:

AN:

151722

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000121

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.00000290

AC:

AN:

1379004

Hom.:

Cov.:

AF XY:

0.00000294

AC XY:

AN XY:

680030

show subpopulations

Gnomad4 AFR exome

AF:

0.0000961

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:

0.0000174

GnomAD4 genome

AF:

0.0000330

AC:

AN:

151722

Hom.:

Cov.:

AF XY:

0.0000270

AC XY:

AN XY:

74086

show subpopulations

Gnomad4 AFR

AF:

0.000121

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000529

ExAC

AF:

0.0000154

AC:

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

Jan 18, 2023

The c.787G>T (p.G263C) alteration is located in exon 1 (coding exon 1) of the BTBD11 gene. This alteration results from a G to T substitution at nucleotide position 787, causing the glycine (G) at amino acid position 263 to be replaced by a cysteine (C). 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

0.12

BayesDel_addAF

Benign

-0.10

BayesDel_noAF

Benign

-0.39

CADD

Uncertain

DANN

Uncertain

0.99

DEOGEN2

Benign

0.0062

T;.;.

Eigen

Benign

-0.15

Eigen_PC

Benign

0.013

FATHMM_MKL

Benign

0.44

LIST_S2

Benign

0.74

T;T;T

M_CAP

Benign

0.074

MetaRNN

Benign

0.098

T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.1

M;M;M

MutationTaster

Benign

0.65

D;D;D

PrimateAI

Pathogenic

0.82

PROVEAN

Benign

-0.83

N;N;N

REVEL

Benign

0.093

Sift

Uncertain

0.0030

D;D;D

Sift4G

Benign

0.080

T;T;T

Polyphen

0.0060

B;B;B

Vest4

0.30

MVP

0.17

MPC

1.1

ClinPred

0.50

GERP RS

4.2

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.26

gMVP

0.27

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