chr3-127676557-G-T

Position:

• chr3-127676557-G-T

Variant summary

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

The ENST00000232744.13(ABTB1):​c.502G>T​(p.Ala168Ser) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/21 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: ABTB1 ENST00000232744.13 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.79

Genes affected

ABTB1 (HGNC:18275): (ankyrin repeat and BTB domain containing 1) This gene encodes a protein with an ankyrin repeat region and two BTB/POZ domains, which are thought to be involved in protein-protein interactions. Expression of this gene is activated by the phosphatase and tensin homolog, a tumor suppressor. Alternate splicing results in three transcript variants. [provided by RefSeq, Mar 2010]

ABTB1 (HGNC:):

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=0.18507907).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ABTB1	NM_172027.3	c.502G>T	p.Ala168Ser	missense_variant	6/12	ENST00000232744.13	NP_742024.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ABTB1	ENST00000232744.13	c.502G>T	p.Ala168Ser	missense_variant	6/12	1	NM_172027.3	ENSP00000232744.8

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 33

Asia WGS AF: 0.000289 AC: 1 AN: 3478

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

Apr 07, 2022

The c.502G>T (p.A168S) alteration is located in exon 6 (coding exon 6) of the ABTB1 gene. This alteration results from a G to T substitution at nucleotide position 502, causing the alanine (A) at amino acid position 168 to be replaced by a serine (S). 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	0.099
BayesDel_addAF	Benign	-0.10	T
BayesDel_noAF	Benign	-0.38
CADD	Benign	21
DANN	Benign	0.88
DEOGEN2	Benign	0.20	T;.;.
Eigen	Benign	-0.24
Eigen_PC	Benign	-0.075
FATHMM_MKL	Uncertain	0.82	D
LIST_S2	Benign	0.73	T;.;T
M_CAP	Benign	0.021	T
MetaRNN	Benign	0.19	T;T;T
MetaSVM	Benign	-0.96	T
MutationAssessor	Benign	0.86	L;.;.
MutationTaster	Benign	0.99	D;D;D;D
PrimateAI	Benign	0.44	T
PROVEAN	Benign	-0.24	N;N;N
REVEL	Benign	0.10
Sift	Benign	0.59	T;T;T
Sift4G	Benign	0.59	T;T;T
Polyphen		0.099	B;.;.
Vest4		0.24
MutPred		0.64		Gain of helix (P = 0.0117);.;.;
MVP		0.49
MPC		0.24
ClinPred		0.44	T
GERP RS		3.5
Varity_R		0.057
gMVP		0.36

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs1576446421; hg19: chr3-127395400;