12-107319305-G-A

Position:

• chr12-107319305-G-A

Variant summary

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

The NM_001018072.2(ABTB3):​c.365G>A​(p.Gly122Asp) 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: 33)
• Consequence: ABTB3 NM_001018072.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.852

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=0.10041672).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ABTB3	NM_001018072.2	c.365G>A	p.Gly122Asp	missense_variant	1/17	ENST00000280758.10
ABTB3	NM_001347943.2	c.365G>A	p.Gly122Asp	missense_variant	1/15
ABTB3	XM_047428301.1	c.365G>A	p.Gly122Asp	missense_variant	1/16

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ABTB3	ENST00000280758.10	c.365G>A	p.Gly122Asp	missense_variant	1/17	5	NM_001018072.2
ABTB3	ENST00000490090.6	c.365G>A	p.Gly122Asp	missense_variant	1/15	2
ABTB3	ENST00000420571.6	c.365G>A	p.Gly122Asp	missense_variant	1/15	5

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 33

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

Jun 21, 2023

The c.365G>A (p.G122D) alteration is located in exon 1 (coding exon 1) of the BTBD11 gene. This alteration results from a G to A substitution at nucleotide position 365, causing the glycine (G) at amino acid position 122 to be replaced by an aspartic acid (D). 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	0.17
BayesDel_addAF	Benign	-0.12	T
BayesDel_noAF	Benign	-0.40
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Benign	0.0064	T;.;.
Eigen	Benign	-0.19
Eigen_PC	Benign	-0.067
FATHMM_MKL	Uncertain	0.86	D
LIST_S2	Benign	0.72	T;T;T
M_CAP	Benign	0.018	T
MetaRNN	Benign	0.10	T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.0	N;N;N
MutationTaster	Benign	0.86	D;D;D
PrimateAI	Uncertain	0.67	T
PROVEAN	Benign	0.21	N;N;N
REVEL	Benign	0.078
Sift	Benign	0.33	T;T;T
Sift4G	Benign	0.13	T;T;T
Polyphen		0.28	B;P;B
Vest4		0.23
MutPred		0.24		Gain of catalytic residue at L124 (P = 0.0377);Gain of catalytic residue at L124 (P = 0.0377);Gain of catalytic residue at L124 (P = 0.0377);
MVP		0.36
MPC		1.4
ClinPred		0.29	T
GERP RS		3.9
Varity_R		0.23
gMVP		0.47

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: chr12-107713082;