12-107319754-C-G

Variant summary

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

The NM_001018072.2(ABTB3):c.814C>G(p.Pro272Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000294 in 1,358,912 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 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)
  • Exomes 𝑓: 0.0000029 (0 hom.)
• Consequence: ABTB3 NM_001018072.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.462

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=0.0963898).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ABTB3	NM_001018072.2	c.814C>G	p.Pro272Ala	missense_variant	1/17	ENST00000280758.10
ABTB3	NM_001347943.2	c.814C>G	p.Pro272Ala	missense_variant	1/15
ABTB3	XM_047428301.1	c.814C>G	p.Pro272Ala	missense_variant	1/16

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ABTB3	ENST00000280758.10	c.814C>G	p.Pro272Ala	missense_variant	1/17	5	NM_001018072.2
ABTB3	ENST00000490090.6	c.814C>G	p.Pro272Ala	missense_variant	1/15	2
ABTB3	ENST00000420571.6	c.814C>G	p.Pro272Ala	missense_variant	1/15	5

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 0.00000294 AC: 4 AN: 1358912 Hom.: 0 Cov.: 32 AF XY: 0.00000149 AC XY: 1 AN XY: 669316

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

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: 0.00000375

Gnomad4 OTH exome AF: 0.00

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

Jan 26, 2022

The c.814C>G (p.P272A) alteration is located in exon 1 (coding exon 1) of the BTBD11 gene. This alteration results from a C to G substitution at nucleotide position 814, causing the proline (P) at amino acid position 272 to be replaced by an alanine (A). 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	0.056
BayesDel_addAF	Benign	-0.13	T
BayesDel_noAF	Benign	-0.42
Cadd	Benign	19
Dann	Benign	0.90
DEOGEN2	Benign	0.0064	T;.;.
Eigen	Benign	-0.88
Eigen_PC	Benign	-0.83
FATHMM_MKL	Benign	0.31	N
LIST_S2	Benign	0.65	T;T;T
M_CAP	Benign	0.071	D
MetaRNN	Benign	0.096	T;T;T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	0.55	N;N;N
MutationTaster	Benign	1.0	N;N;N
PrimateAI	Uncertain	0.77	T
PROVEAN	Benign	-0.56	N;N;N
REVEL	Benign	0.069
Sift	Pathogenic	0.0	D;D;D
Sift4G	Benign	0.33	T;T;T
Polyphen		0.088	B;B;B
Vest4		0.21
MutPred		0.18		Gain of catalytic residue at G273 (P = 2e-04);Gain of catalytic residue at G273 (P = 2e-04);Gain of catalytic residue at G273 (P = 2e-04);
MVP		0.19
MPC		1.0
ClinPred		0.17	T
GERP RS		1.6
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.11
gMVP		0.088

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: chr12-107713531;