12-107319296-C-T

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2 BP4_Strong BP6_Moderate

The NM_001018072.2(ABTB3):c.356C>T(p.Ala119Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000719 in 1,390,716 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 7.2e-7 (0 hom.)
• Consequence: ABTB3 NM_001018072.2 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.341

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 Likely_benign. Variant got -4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.050488263).
• BP6: Variant 12-107319296-C-T is Benign according to our data. Variant chr12-107319296-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 3133224.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ABTB3	NM_001018072.2	c.356C>T	p.Ala119Val	missense_variant	1/17	ENST00000280758.10
ABTB3	NM_001347943.2	c.356C>T	p.Ala119Val	missense_variant	1/15
ABTB3	XM_047428301.1	c.356C>T	p.Ala119Val	missense_variant	1/16

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ABTB3	ENST00000280758.10	c.356C>T	p.Ala119Val	missense_variant	1/17	5	NM_001018072.2
ABTB3	ENST00000490090.6	c.356C>T	p.Ala119Val	missense_variant	1/15	2
ABTB3	ENST00000420571.6	c.356C>T	p.Ala119Val	missense_variant	1/15	5

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD3 exomes AF: 0.00000727 AC: 1 AN: 137548 Hom.: 0 AF XY: 0.0000133 AC XY: 1 AN XY: 75470

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000929

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 7.19e-7 AC: 1 AN: 1390716 Hom.: 0 Cov.: 33 AF XY: 0.00000146 AC XY: 1 AN XY: 686512

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000278

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 08, 2023

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.079
BayesDel_addAF	Benign	-0.43	T
BayesDel_noAF	Benign	-0.65
Cadd	Benign	13
Dann	Uncertain	0.98
DEOGEN2	Benign	0.0054	T;.;.
Eigen	Benign	-0.98
Eigen_PC	Benign	-0.96
FATHMM_MKL	Benign	0.090	N
LIST_S2	Benign	0.68	T;T;T
M_CAP	Benign	0.011	T
MetaRNN	Benign	0.050	T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.90	L;L;L
MutationTaster	Benign	1.0	N;N;N
PrimateAI	Uncertain	0.60	T
PROVEAN	Benign	-0.34	N;N;N
REVEL	Benign	0.076
Sift	Benign	0.39	T;T;T
Sift4G	Benign	0.64	T;T;T
Polyphen		0.0010	B;B;B
Vest4		0.024
MutPred		0.26		Gain of catalytic residue at A116 (P = 2e-04);Gain of catalytic residue at A116 (P = 2e-04);Gain of catalytic residue at A116 (P = 2e-04);
MVP		0.27
MPC		1.1
ClinPred		0.060	T
GERP RS		-1.5
Varity_R		0.035
gMVP		0.18

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

Other links and lift over

dbSNP: rs753593336; hg19: chr12-107713073;