Variant 8-144440133-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_013432.5(TONSL):c.1368A>G(p.Leu456=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.981 in 1,612,168 control chromosomes in the GnomAD database, including 778,122 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Synonymous variant affecting the same amino acid position (i.e. L456L) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.95 ( 69488 hom., cov: 34)

Exomes 𝑓: 0.98 ( 708634 hom. )

Consequence

TONSL
NM_013432.5 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 1.18

Variant links:

Genes affected

TONSL (HGNC:7801): (tonsoku like, DNA repair protein) The protein encoded by this gene is thought to be a negative regulator of NF-kappa-B mediated transcription. The encoded protein may bind NF-kappa-B complexes and trap them in the cytoplasm, preventing them from entering the nucleus and interacting with the DNA. Phosphorylation of this protein targets it for degradation by the ubiquitination pathway, which frees the NF-kappa-B complexes to enter the nucleus. [provided by RefSeq, Jul 2008]

TONSL links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.69).

BP6

Variant 8-144440133-T-C is Benign according to our data. Variant chr8-144440133-T-C is described in ClinVar as [Benign]. Clinvar id is 1167023.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=1.18 with no splicing effect.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.991 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
TONSL	NM_013432.5 linkuse as main transcript	c.1368A>G	p.Leu456=	synonymous_variant	11/26	ENST00000409379.8
TONSL	XM_011517048.3 linkuse as main transcript	c.396A>G	p.Leu132=	synonymous_variant	4/19
TONSL	XM_011517049.3 linkuse as main transcript	c.360A>G	p.Leu120=	synonymous_variant	4/19
TONSL	XM_011517050.3 linkuse as main transcript	c.1368A>G	p.Leu456=	synonymous_variant	11/19

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TONSL	ENST00000409379.8 linkuse as main transcript	c.1368A>G	p.Leu456=	synonymous_variant	11/26	1	NM_013432.5	P1	Q96HA7-1
TONSL	ENST00000497613.2 linkuse as main transcript	n.2343A>G		non_coding_transcript_exon_variant	3/17	2

Frequencies

GnomAD3 genomes

AF:

0.954

AC:

145145

AN:

152188

Hom.:

69453

Cov.:

show subpopulations

Gnomad AFR

AF:

0.894

Gnomad AMI

AF:

1.00

Gnomad AMR

AF:

0.921

Gnomad ASJ

AF:

0.987

Gnomad EAS

AF:

0.800

Gnomad SAS

AF:

0.996

Gnomad FIN

AF:

0.997

Gnomad MID

AF:

0.987

Gnomad NFE

AF:

0.997

Gnomad OTH

AF:

0.964

GnomAD3 exomes

AF:

0.958

AC:

236071

AN:

246478

Hom.:

113636

AF XY:

0.966

AC XY:

129527

AN XY:

134120

show subpopulations

Gnomad AFR exome

AF:

0.892

Gnomad AMR exome

AF:

0.881

Gnomad ASJ exome

AF:

0.988

Gnomad EAS exome

AF:

0.789

Gnomad SAS exome

AF:

0.998

Gnomad FIN exome

AF:

0.996

Gnomad NFE exome

AF:

0.997

Gnomad OTH exome

AF:

0.976

GnomAD4 exome

AF:

0.984

AC:

1436730

AN:

1459862

Hom.:

708634

Cov.:

AF XY:

0.985

AC XY:

715670

AN XY:

726304

show subpopulations

Gnomad4 AFR exome

AF:

0.894

Gnomad4 AMR exome

AF:

0.887

Gnomad4 ASJ exome

AF:

0.988

Gnomad4 EAS exome

AF:

0.756

Gnomad4 SAS exome

AF:

0.997

Gnomad4 FIN exome

AF:

0.995

Gnomad4 NFE exome

AF:

0.997

Gnomad4 OTH exome

AF:

0.980

GnomAD4 genome

AF:

0.954

AC:

145232

AN:

152306

Hom.:

69488

Cov.:

AF XY:

0.952

AC XY:

70910

AN XY:

74480

show subpopulations

Gnomad4 AFR

AF:

0.894

Gnomad4 AMR

AF:

0.920

Gnomad4 ASJ

AF:

0.987

Gnomad4 EAS

AF:

0.799

Gnomad4 SAS

AF:

0.996

Gnomad4 FIN

AF:

0.997

Gnomad4 NFE

AF:

0.997

Gnomad4 OTH

AF:

0.964

Alfa

AF:

0.981

Hom.:

32839

Bravo

AF:

0.944

Asia WGS

AF:

0.932

AC:

3243

AN:

3478

EpiCase

AF:

0.997

EpiControl

AF:

0.997

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Feb 01, 2024	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Apr 13, 2020	- -

Sponastrime dysplasia

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Sep 10, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.69

CADD

Benign

2.5

DANN

Benign

0.42

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.8

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