Variant 12-107319398-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3

The NM_001018072.2(ABTB3):c.458G>C(p.Arg153Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000939 in 1,596,794 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 0.000020 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0000083 ( 0 hom. )

Consequence

ABTB3
NM_001018072.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.95

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 3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.804

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
ABTB3	NM_001018072.2 linkuse as main transcript	c.458G>C	p.Arg153Pro	missense_variant	1/17	ENST00000280758.10
ABTB3	NM_001347943.2 linkuse as main transcript	c.458G>C	p.Arg153Pro	missense_variant	1/15
ABTB3	XM_047428301.1 linkuse as main transcript	c.458G>C	p.Arg153Pro	missense_variant	1/16

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	UniProt
ABTB3	ENST00000280758.10 linkuse as main transcript	c.458G>C	p.Arg153Pro	missense_variant	1/17	5	NM_001018072.2	A6QL63-1
ABTB3	ENST00000490090.6 linkuse as main transcript	c.458G>C	p.Arg153Pro	missense_variant	1/15	2		A6QL63-3
ABTB3	ENST00000420571.6 linkuse as main transcript	c.458G>C	p.Arg153Pro	missense_variant	1/15	5		A6QL63-2

Frequencies

GnomAD3 genomes

AF:

0.0000197

AC:

AN:

152156

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

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:

0.0000441

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000428

AC:

AN:

210324

Hom.:

AF XY:

0.0000431

AC XY:

AN XY:

116050

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000627

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:

0.0000667

Gnomad OTH exome

AF:

0.000185

GnomAD4 exome

AF:

0.00000831

AC:

AN:

1444638

Hom.:

Cov.:

AF XY:

0.0000111

AC XY:

AN XY:

717586

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000234

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:

0.00000905

Gnomad4 OTH exome

AF:

0.0000167

GnomAD4 genome

AF:

0.0000197

AC:

AN:

152156

Hom.:

Cov.:

AF XY:

0.0000269

AC XY:

AN XY:

74308

show subpopulations

Gnomad4 AFR

AF:

0.00

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:

0.0000441

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000566

Hom.:

Bravo

AF:

0.0000264

ExAC

AF:

0.0000167

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

Jun 24, 2022

The c.458G>C (p.R153P) alteration is located in exon 1 (coding exon 1) of the BTBD11 gene. This alteration results from a G to C substitution at nucleotide position 458, causing the arginine (R) at amino acid position 153 to be replaced by a proline (P). 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

0.67

BayesDel_addAF

Pathogenic

0.28

BayesDel_noAF

Pathogenic

0.34

Cadd

Pathogenic

Dann

Benign

0.95

DEOGEN2

Benign

0.020

T;.;.

Eigen

Uncertain

0.47

Eigen_PC

Uncertain

0.46

FATHMM_MKL

Uncertain

0.90

LIST_S2

Uncertain

0.95

D;D;D

M_CAP

Uncertain

0.24

MetaRNN

Pathogenic

0.80

D;D;D

MetaSVM

Uncertain

0.57

MutationAssessor

Benign

1.9

L;L;L

MutationTaster

Benign

1.0

D;D;D

PrimateAI

Uncertain

0.72

PROVEAN

Benign

0.46

N;N;N

REVEL

Uncertain

0.63

Sift

Benign

0.42

T;T;T

Sift4G

Benign

0.37

T;T;T

Polyphen

1.0

D;D;D

Vest4

0.71

MutPred

0.45

Loss of MoRF binding (P = 0.0016);Loss of MoRF binding (P = 0.0016);Loss of MoRF binding (P = 0.0016);

MVP

0.83

MPC

1.5

ClinPred

0.14

GERP RS

4.7

Varity_R

0.41

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