12-107319781-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001018072.2(ABTB3):c.841G>C(p.Ala281Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 31)
• Consequence: ABTB3 NM_001018072.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.34

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]

ACMG classification

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=0.13071156).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ABTB3	NM_001018072.2	c.841G>C	p.Ala281Pro	missense_variant	1/17	ENST00000280758.10
ABTB3	NM_001347943.2	c.841G>C	p.Ala281Pro	missense_variant	1/15
ABTB3	XM_047428301.1	c.841G>C	p.Ala281Pro	missense_variant	1/16

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ABTB3	ENST00000280758.10	c.841G>C	p.Ala281Pro	missense_variant	1/17	5	NM_001018072.2
ABTB3	ENST00000490090.6	c.841G>C	p.Ala281Pro	missense_variant	1/15	2
ABTB3	ENST00000420571.6	c.841G>C	p.Ala281Pro	missense_variant	1/15	5

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 27

GnomAD4 genome Cov.: 31

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 28, 2023

The c.841G>C (p.A281P) 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 841, causing the alanine (A) at amino acid position 281 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	Benign	0.079
BayesDel_addAF	Benign	-0.15	T
BayesDel_noAF	Benign	-0.45
Cadd	Benign	20
Dann	Uncertain	0.99
DEOGEN2	Benign	0.0055	T;.;.
Eigen	Benign	-0.44
Eigen_PC	Benign	-0.30
FATHMM_MKL	Benign	0.68	D
LIST_S2	Benign	0.64	T;T;T
M_CAP	Uncertain	0.085	D
MetaRNN	Benign	0.13	T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.90	L;L;L
MutationTaster	Benign	1.0	N;N;N
PrimateAI	Pathogenic	0.87	D
PROVEAN	Benign	-0.24	N;N;N
REVEL	Benign	0.039
Sift	Uncertain	0.010	D;D;D
Sift4G	Benign	0.33	T;T;T
Polyphen		0.0010	B;B;B
Vest4		0.20
MutPred		0.23		Gain of catalytic residue at A281 (P = 6e-04);Gain of catalytic residue at A281 (P = 6e-04);Gain of catalytic residue at A281 (P = 6e-04);
MVP		0.17
MPC		1.4
ClinPred		0.51	D
GERP RS		3.5
Varity_R		0.20
gMVP		0.10

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.

Other links and lift over

hg19: chr12-107713558;