Variant 14-95691296-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_004918.4(TCL1B):c.362C>T(p.Thr121Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000958 in 1,461,422 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 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: 0.0000096 ( 0 hom. )

Consequence

TCL1B
NM_004918.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -1.25

Variant links:

Genes affected

TCL1B (HGNC:11649): (TCL1 family AKT coactivator B) Enables protein kinase binding activity and protein serine/threonine kinase activator activity. Involved in positive regulation of peptidyl-serine phosphorylation and positive regulation of protein serine/threonine kinase activity. Part of protein-containing complex. [provided by Alliance of Genome Resources, Apr 2022]

TCL1B links:

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ACMG classification

Classification made for transcript

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=0.14747623).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TCL1B	NM_004918.4 linkuse as main transcript	c.362C>T	p.Thr121Ile	missense_variant	3/4	ENST00000340722.8	NP_004909.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris
TCL1B	ENST00000340722.8 linkuse as main transcript	c.362C>T	p.Thr121Ile	missense_variant	3/4	1	NM_004918.4	ENSP00000343223	P1
TCL1B	ENST00000464815.5 linkuse as main transcript	n.392C>T		non_coding_transcript_exon_variant	3/3	1
TCL1B	ENST00000556665.1 linkuse as main transcript	n.322C>T		non_coding_transcript_exon_variant	3/3	2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000399

AC:

AN:

250742

Hom.:

AF XY:

0.00

AC XY:

AN XY:

135424

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000290

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

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:

0.00000958

AC:

AN:

1461422

Hom.:

Cov.:

AF XY:

0.00000825

AC XY:

AN XY:

726906

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000179

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:

8.99e-7

Gnomad4 OTH exome

AF:

0.0000828

GnomAD4 genome

Cov.:

Bravo

AF:

0.0000113

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jun 18, 2021

The c.362C>T (p.T121I) alteration is located in exon 3 (coding exon 3) of the TCL1B gene. This alteration results from a C to T substitution at nucleotide position 362, causing the threonine (T) at amino acid position 121 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

Benign

0.20

BayesDel_addAF

Benign

-0.33

BayesDel_noAF

Benign

-0.63

CADD

Benign

1.9

DANN

Uncertain

0.99

DEOGEN2

Benign

0.018

Eigen

Benign

-0.93

Eigen_PC

Benign

-1.2

FATHMM_MKL

Benign

0.0035

LIST_S2

Benign

0.42

M_CAP

Benign

0.0026

MetaRNN

Benign

0.15

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.4

MutationTaster

Benign

1.0

PrimateAI

Benign

0.36

PROVEAN

Benign

-1.7

REVEL

Benign

0.055

Sift

Benign

0.086

Sift4G

Benign

0.10

Polyphen

0.73

Vest4

0.17

MutPred

0.48

Loss of glycosylation at T121 (P = 0.0618);

MVP

0.092

MPC

0.55

ClinPred

0.42

GERP RS

-4.3

Varity_R

0.17

gMVP

0.090

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over