12-107319275-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.335G>C(p.Arg112Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000717 in 1,394,890 control chromosomes in the GnomAD database, with no homozygous occurrence. 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)
  • Exomes 𝑓: 7.2e-7 (0 hom.)
• Consequence: ABTB3 NM_001018072.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.57

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=0.13461778).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ABTB3	NM_001018072.2	c.335G>C	p.Arg112Pro	missense_variant	1/17	ENST00000280758.10
ABTB3	NM_001347943.2	c.335G>C	p.Arg112Pro	missense_variant	1/15
ABTB3	XM_047428301.1	c.335G>C	p.Arg112Pro	missense_variant	1/16

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ABTB3	ENST00000280758.10	c.335G>C	p.Arg112Pro	missense_variant	1/17	5	NM_001018072.2
ABTB3	ENST00000490090.6	c.335G>C	p.Arg112Pro	missense_variant	1/15	2
ABTB3	ENST00000420571.6	c.335G>C	p.Arg112Pro	missense_variant	1/15	5

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 7.17e-7 AC: 1 AN: 1394890 Hom.: 0 Cov.: 33 AF XY: 0.00000145 AC XY: 1 AN XY: 689174

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: 9.24e-7

Gnomad4 OTH exome AF: 0.00

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

Aug 11, 2022

The c.335G>C (p.R112P) 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 335, causing the arginine (R) at amino acid position 112 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	0.11
BayesDel_addAF	Benign	-0.12	T
BayesDel_noAF	Benign	-0.41
Cadd	Uncertain	24
Dann	Uncertain	0.99
DEOGEN2	Benign	0.032	T;.;.
Eigen	Benign	-0.012
Eigen_PC	Benign	0.14
FATHMM_MKL	Benign	0.75	D
LIST_S2	Benign	0.65	T;T;T
M_CAP	Benign	0.031	D
MetaRNN	Benign	0.13	T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.6	L;L;L
MutationTaster	Benign	0.81	N;N;N
PrimateAI	Uncertain	0.74	T
PROVEAN	Benign	-1.7	N;N;N
REVEL	Benign	0.055
Sift	Uncertain	0.014	D;D;D
Sift4G	Benign	0.062	T;T;T
Polyphen		0.0010	B;B;B
Vest4		0.27
MutPred		0.30		Gain of catalytic residue at A116 (P = 9e-04);Gain of catalytic residue at A116 (P = 9e-04);Gain of catalytic residue at A116 (P = 9e-04);
MVP		0.13
MPC		1.5
ClinPred		0.93	D
GERP RS		4.9
Varity_R		0.49
gMVP		0.66

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: chr12-107713052;