chr1-151088290-C-T

Position:

• chr1-151088290-C-T

Variant summary

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

The NM_144618.3(GABPB2):​c.101C>T​(p.Thr34Ile) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. T34A) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: GABPB2 NM_144618.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.84

Genes affected

GABPB2 (HGNC:28441): (GA binding protein transcription factor subunit beta 2) Enables transcription cis-regulatory region binding activity. Acts upstream of or within positive regulation of transcription by RNA polymerase II. Located in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GABPB2	NM_144618.3	c.101C>T	p.Thr34Ile	missense_variant	2/9	ENST00000368918.8	NP_653219.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GABPB2	ENST00000368918.8	c.101C>T	p.Thr34Ile	missense_variant	2/9	1	NM_144618.3	ENSP00000357914.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 29

GnomAD4 genome Cov.: 32

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

Oct 16, 2024

The c.101C>T (p.T34I) alteration is located in exon 2 (coding exon 1) of the GABPB2 gene. This alteration results from a C to T substitution at nucleotide position 101, causing the threonine (T) at amino acid position 34 to be replaced by an isoleucine (I). 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	Pathogenic	0.96
BayesDel_addAF	Uncertain	0.065	T
BayesDel_noAF	Benign	-0.14
CADD	Pathogenic	28
DANN	Uncertain	1.0
DEOGEN2	Benign	0.22	T;T
Eigen	Uncertain	0.68
Eigen_PC	Pathogenic	0.72
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.96	D;D
M_CAP	Benign	0.022	T
MetaRNN	Uncertain	0.63	D;D
MetaSVM	Benign	-0.91	T
MutationAssessor	Benign	0.53	N;.
PrimateAI	Pathogenic	0.91	D
PROVEAN	Pathogenic	-5.1	D;D
REVEL	Uncertain	0.35
Sift	Uncertain	0.015	D;D
Sift4G	Uncertain	0.0020	D;D
Polyphen		1.0	D;.
Vest4		0.70
MutPred		0.39		Loss of phosphorylation at T34 (P = 0.0452);Loss of phosphorylation at T34 (P = 0.0452);
MVP		0.65
MPC		0.65
ClinPred		0.99	D
GERP RS		5.4
Varity_R		0.55
gMVP		0.68

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: chr1-151060766;