NM_144618.3:c.101C>T

Variant names:

• chr1-151088290-C-T
• NM_144618.3:c.101C>T

Variant summary

Our verdict is Uncertain significance. The variant received 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
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_144618.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GABPB2	NM_144618.3	MANE Select	c.101C>T	p.Thr34Ile	missense	Exon 2 of 9	NP_653219.1	Q8TAK5
	GABPB2	NM_001323910.2		c.101C>T	p.Thr34Ile	missense	Exon 2 of 10	NP_001310839.1
	GABPB2	NM_001323906.2		c.101C>T	p.Thr34Ile	missense	Exon 2 of 10	NP_001310835.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GABPB2	ENST00000368918.8	TSL:1 MANE Select	c.101C>T	p.Thr34Ile	missense	Exon 2 of 9	ENSP00000357914.3	Q8TAK5
	GABPB2	ENST00000931884.1		c.101C>T	p.Thr34Ile	missense	Exon 2 of 10	ENSP00000601943.1
	GABPB2	ENST00000947109.1		c.101C>T	p.Thr34Ile	missense	Exon 2 of 10	ENSP00000617168.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 29

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

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
Eigen	Uncertain	0.68
Eigen_PC	Pathogenic	0.72
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.96	D
M_CAP	Benign	0.022	T
MetaRNN	Uncertain	0.63	D
MetaSVM	Benign	-0.91	T
MutationAssessor	Benign	0.53	N
PhyloP100		7.8
PrimateAI	Pathogenic	0.91	D
PROVEAN	Pathogenic	-5.1	D
REVEL	Uncertain	0.35
Sift	Uncertain	0.015	D
Sift4G	Uncertain	0.0020	D
Polyphen		1.0	D
Vest4		0.70
MutPred		0.39		Loss of phosphorylation at T34 (P = 0.0452)
MVP		0.65
MPC		0.65
ClinPred		0.99	D
GERP RS		5.4
PromoterAI		-0.048	Neutral
Varity_R		0.55
gMVP		0.68
Mutation Taster		=38/62	disease causing

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

Other links and lift over

hg19: chr1-151060766;