Variant 14-95686606-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_004918.4(TCL1B):c.139G>C(p.Ala47Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000116 in 1,459,320 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: 32)

Exomes 𝑓: 0.000012 ( 0 hom. )

Consequence

TCL1B
NM_004918.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.216

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 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.34330896).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TCL1B	NM_004918.4 linkuse as main transcript	c.139G>C	p.Ala47Pro	missense_variant	1/4	ENST00000340722.8	NP_004909.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TCL1B	ENST00000340722.8 linkuse as main transcript	c.139G>C	p.Ala47Pro	missense_variant	1/4	1	NM_004918.4	ENSP00000343223	P1
TCL1B	ENST00000464815.5 linkuse as main transcript	n.169G>C		non_coding_transcript_exon_variant	1/3	1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000808

AC:

AN:

247502

Hom.:

AF XY:

0.00

AC XY:

AN XY:

133940

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

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:

0.0000180

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000116

AC:

AN:

1459320

Hom.:

Cov.:

AF XY:

0.00000827

AC XY:

AN XY:

725930

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

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:

0.0000153

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000285

Hom.:

Bravo

AF:

0.00000756

ExAC

AF:

0.00000824

AC:

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

Jan 24, 2023

The c.139G>C (p.A47P) alteration is located in exon 1 (coding exon 1) of the TCL1B gene. This alteration results from a G to C substitution at nucleotide position 139, causing the alanine (A) at amino acid position 47 to be replaced by a proline (P). 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

0.10

BayesDel_addAF

Benign

-0.27

BayesDel_noAF

Benign

-0.56

CADD

Benign

6.6

DANN

Uncertain

0.99

DEOGEN2

Benign

0.011

Eigen

Benign

-0.71

Eigen_PC

Benign

-0.91

FATHMM_MKL

Benign

0.077

LIST_S2

Benign

0.44

M_CAP

Benign

0.0037

MetaRNN

Benign

0.34

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.4

MutationTaster

Benign

1.0

PrimateAI

Benign

0.26

PROVEAN

Benign

-1.1

REVEL

Benign

0.13

Sift

Benign

0.18

Sift4G

Benign

0.27

Polyphen

0.93

Vest4

0.27

MutPred

0.75

Gain of glycosylation at A47 (P = 0.0307);

MVP

0.12

MPC

0.66

ClinPred

0.16

GERP RS

-0.60

Varity_R

0.15

gMVP

0.34

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

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