chr8-144438491-C-T

Position:

chr8-144438491-C-T

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 2P and 10B. PM2BP4_StrongBP6_ModerateBS1

The ENST00000409379.8(TONSL):c.1633G>A(p.Val545Ile) variant causes a missense change. The variant allele was found at a frequency of 0.000172 in 1,613,002 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00032 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00016 ( 0 hom. )

Consequence

TONSL
ENST00000409379.8 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 3.92

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:

TONSL-AS1 (HGNC:51556): (TONSL antisense RNA 1)

TONSL-AS1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.01001811).

BP6

Variant 8-144438491-C-T is Benign according to our data. Variant chr8-144438491-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 1658833.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population eas. gnomad4 allele frequency = 0.000315 (48/152352) while in subpopulation EAS AF= 0.00501 (26/5188). AF 95% confidence interval is 0.00351. There are 0 homozygotes in gnomad4. There are 26 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TONSL	NM_013432.5 linkuse as main transcript	c.1633G>A	p.Val545Ile	missense_variant	13/26	ENST00000409379.8	NP_038460.4
TONSL-AS1	NR_109770.1 linkuse as main transcript	n.672+158C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TONSL	ENST00000409379.8 linkuse as main transcript	c.1633G>A	p.Val545Ile	missense_variant	13/26	1	NM_013432.5	ENSP00000386239	P1	Q96HA7-1
TONSL-AS1	ENST00000442850.1 linkuse as main transcript	n.178+158C>T		intron_variant, non_coding_transcript_variant		5
TONSL	ENST00000497613.2 linkuse as main transcript	n.2608G>A		non_coding_transcript_exon_variant	5/17	2

Frequencies

GnomAD3 genomes

AF:

0.000315

AC:

AN:

152234

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000965

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000523

Gnomad ASJ

AF:

0.00259

Gnomad EAS

AF:

0.00500

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.000429

AC:

107

AN:

249400

Hom.:

AF XY:

0.000406

AC XY:

AN XY:

135394

show subpopulations

Gnomad AFR exome

AF:

0.000125

Gnomad AMR exome

AF:

0.000145

Gnomad ASJ exome

AF:

0.00150

Gnomad EAS exome

AF:

0.00382

Gnomad SAS exome

AF:

0.0000981

Gnomad FIN exome

AF:

0.0000466

Gnomad NFE exome

AF:

0.0000712

Gnomad OTH exome

AF:

0.000492

GnomAD4 exome

AF:

0.000157

AC:

230

AN:

1460650

Hom.:

Cov.:

AF XY:

0.000169

AC XY:

123

AN XY:

726694

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000112

Gnomad4 ASJ exome

AF:

0.00191

Gnomad4 EAS exome

AF:

0.00310

Gnomad4 SAS exome

AF:

0.0000696

Gnomad4 FIN exome

AF:

0.0000382

Gnomad4 NFE exome

AF:

0.0000216

Gnomad4 OTH exome

AF:

0.000315

GnomAD4 genome

AF:

0.000315

AC:

AN:

152352

Hom.:

Cov.:

AF XY:

0.000349

AC XY:

AN XY:

74502

show subpopulations

Gnomad4 AFR

AF:

0.0000962

Gnomad4 AMR

AF:

0.000523

Gnomad4 ASJ

AF:

0.00259

Gnomad4 EAS

AF:

0.00501

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.000473

Alfa

AF:

0.000174

Hom.:

Bravo

AF:

0.000484

ESP6500AA

AF:

0.000454

AC:

ESP6500EA

AF:

0.000233

AC:

ExAC

AF:

0.000313

AC:

Asia WGS

AF:

0.00115

AC:

AN:

3478

EpiCase

AF:

0.00

EpiControl

AF:

0.0000593

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 29, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.20

BayesDel_addAF

Benign

-0.36

BayesDel_noAF

Benign

-0.28

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.13

T;.

Eigen

Benign

0.054

Eigen_PC

Benign

0.092

FATHMM_MKL

Uncertain

0.97

M_CAP

Benign

0.056

MetaRNN

Benign

0.010

T;T

MetaSVM

Benign

-0.82

MutationAssessor

Uncertain

2.4

M;.

MutationTaster

Benign

1.0

PrimateAI

Benign

0.40

PROVEAN

Benign

-0.80

N;.

REVEL

Benign

0.17

Sift

Benign

0.056

T;.

Sift4G

Uncertain

0.014

D;D

Polyphen

0.63

P;.

Vest4

0.35

MVP

0.73

MPC

0.28

ClinPred

0.043

GERP RS

4.2

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.15

gMVP

0.44

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

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