Variant 12-107319482-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.542C>T(p.Ala181Val) variant causes a missense change. The variant allele was found at a frequency of 0.0000463 in 1,597,894 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 0.00025 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000025 ( 0 hom. )

Consequence

ABTB3
NM_001018072.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.85

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=0.103028595).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
ABTB3	NM_001018072.2 linkuse as main transcript	c.542C>T	p.Ala181Val	missense_variant	1/17	ENST00000280758.10
ABTB3	NM_001347943.2 linkuse as main transcript	c.542C>T	p.Ala181Val	missense_variant	1/15
ABTB3	XM_047428301.1 linkuse as main transcript	c.542C>T	p.Ala181Val	missense_variant	1/16

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	UniProt
ABTB3	ENST00000280758.10 linkuse as main transcript	c.542C>T	p.Ala181Val	missense_variant	1/17	5	NM_001018072.2	A6QL63-1
ABTB3	ENST00000490090.6 linkuse as main transcript	c.542C>T	p.Ala181Val	missense_variant	1/15	2		A6QL63-3
ABTB3	ENST00000420571.6 linkuse as main transcript	c.542C>T	p.Ala181Val	missense_variant	1/15	5		A6QL63-2

Frequencies

GnomAD3 genomes

AF:

0.000250

AC:

AN:

152140

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000893

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000654

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

GnomAD3 exomes

AF:

0.0000485

AC:

AN:

206392

Hom.:

AF XY:

0.00000874

AC XY:

AN XY:

114430

show subpopulations

Gnomad AFR exome

AF:

0.000841

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000249

AC:

AN:

1445634

Hom.:

Cov.:

AF XY:

0.0000181

AC XY:

AN XY:

718152

show subpopulations

Gnomad4 AFR exome

AF:

0.000995

Gnomad4 AMR exome

AF:

0.0000232

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:

0.0000335

GnomAD4 genome

AF:

0.000250

AC:

AN:

152260

Hom.:

Cov.:

AF XY:

0.000309

AC XY:

AN XY:

74444

show subpopulations

Gnomad4 AFR

AF:

0.000890

Gnomad4 AMR

AF:

0.0000653

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

Alfa

AF:

0.0000680

Hom.:

Bravo

AF:

0.000246

ESP6500AA

AF:

0.000720

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.0000423

AC:

Asia WGS

AF:

0.000578

AC:

AN:

3476

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

Nov 09, 2021

The c.542C>T (p.A181V) 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 542, causing the alanine (A) at amino acid position 181 to be replaced by a valine (V). 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

Uncertain

0.55

BayesDel_addAF

Benign

-0.33

BayesDel_noAF

Benign

-0.28

Cadd

Pathogenic

Dann

Uncertain

1.0

DEOGEN2

Benign

0.34

T;.;.

Eigen

Uncertain

0.52

Eigen_PC

Uncertain

0.49

FATHMM_MKL

Uncertain

0.94

LIST_S2

Benign

0.83

T;T;T

M_CAP

Benign

0.022

MetaRNN

Benign

0.10

T;T;T

MetaSVM

Benign

-0.91

MutationAssessor

Uncertain

2.9

M;M;M

MutationTaster

Benign

1.0

D;D;D

PrimateAI

Uncertain

0.76

PROVEAN

Uncertain

-2.9

D;D;D

REVEL

Benign

0.15

Sift

Uncertain

0.0010

D;D;D

Sift4G

Uncertain

0.020

D;D;D

Polyphen

0.88

P;P;P

Vest4

0.58

MVP

0.36

MPC

1.3

ClinPred

0.54

GERP RS

4.7

Varity_R

0.64

gMVP

0.71

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