Variant 3-127674432-A-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate

The NM_172027.3(ABTB1):c.98A>T(p.Asp33Val) variant causes a missense change. The variant allele was found at a frequency of 0.000414 in 1,610,920 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00021 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00043 ( 0 hom. )

Consequence

ABTB1
NM_172027.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.74

Variant links:

Genes affected

ABTB1 (HGNC:18275): (ankyrin repeat and BTB domain containing 1) This gene encodes a protein with an ankyrin repeat region and two BTB/POZ domains, which are thought to be involved in protein-protein interactions. Expression of this gene is activated by the phosphatase and tensin homolog, a tumor suppressor. Alternate splicing results in three transcript variants. [provided by RefSeq, Mar 2010]

ABTB1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.881

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ABTB1	NM_172027.3 linkuse as main transcript	c.98A>T	p.Asp33Val	missense_variant	2/12	ENST00000232744.13	NP_742024.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ABTB1	ENST00000232744.13 linkuse as main transcript	c.98A>T	p.Asp33Val	missense_variant	2/12	1	NM_172027.3	ENSP00000232744	P1	Q969K4-1

Frequencies

GnomAD3 genomes

AF:

0.000212

AC:

AN:

150944

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000730

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000659

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.0000969

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000384

Gnomad OTH

AF:

0.000483

GnomAD3 exomes

AF:

0.000328

AC:

AN:

249662

Hom.:

AF XY:

0.000222

AC XY:

AN XY:

134976

show subpopulations

Gnomad AFR exome

AF:

0.000124

Gnomad AMR exome

AF:

0.0000870

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000649

Gnomad NFE exome

AF:

0.000532

Gnomad OTH exome

AF:

0.000494

GnomAD4 exome

AF:

0.000435

AC:

635

AN:

1459976

Hom.:

Cov.:

AF XY:

0.000412

AC XY:

299

AN XY:

726260

show subpopulations

Gnomad4 AFR exome

AF:

0.000120

Gnomad4 AMR exome

AF:

0.0000672

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.000414

Gnomad4 NFE exome

AF:

0.000517

Gnomad4 OTH exome

AF:

0.000514

GnomAD4 genome

AF:

0.000212

AC:

AN:

150944

Hom.:

Cov.:

AF XY:

0.000136

AC XY:

AN XY:

73664

show subpopulations

Gnomad4 AFR

AF:

0.0000730

Gnomad4 AMR

AF:

0.0000659

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.0000969

Gnomad4 NFE

AF:

0.000384

Gnomad4 OTH

AF:

0.000483

Alfa

AF:

0.000244

Hom.:

Bravo

AF:

0.000246

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.000259

AC:

ESP6500AA

AF:

0.000454

AC:

ESP6500EA

AF:

0.000233

AC:

ExAC

AF:

0.000420

AC:

EpiCase

AF:

0.000436

EpiControl

AF:

0.000475

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

Aug 02, 2021

The c.98A>T (p.D33V) alteration is located in exon 2 (coding exon 2) of the ABTB1 gene. This alteration results from a A to T substitution at nucleotide position 98, causing the aspartic acid (D) at amino acid position 33 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

Pathogenic

1.0

BayesDel_addAF

Benign

-0.058

BayesDel_noAF

Uncertain

0.020

CADD

Pathogenic

DANN

Uncertain

0.99

DEOGEN2

Benign

0.29

Eigen

Pathogenic

0.79

Eigen_PC

Pathogenic

0.68

FATHMM_MKL

Uncertain

0.97

LIST_S2

Pathogenic

0.98

M_CAP

Pathogenic

0.45

MetaRNN

Pathogenic

0.88

MetaSVM

Uncertain

0.15

MutationAssessor

Pathogenic

3.5

MutationTaster

Benign

1.0

D;D;D;D

PrimateAI

Pathogenic

0.85

PROVEAN

Pathogenic

-7.9

REVEL

Uncertain

0.52

Sift

Pathogenic

0.0

Sift4G

Uncertain

0.0020

Polyphen

1.0

Vest4

0.99

MVP

0.71

MPC

0.53

ClinPred

0.92

GERP RS

4.1

Varity_R

0.90

gMVP

0.87

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.090

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