GeneBe

8-144429161-G-A

Variant names:

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2BP4_StrongBP7

The NM_013432.5(TONSL):​c.4119C>T​(p.Leu1373Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. L1373L) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 33)
Exomes 𝑓: 0.0 ( 0 hom. )
Failed GnomAD Quality Control

Consequence

TONSL
NM_013432.5 synonymous

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.05

Publications

0 publications found
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]
VPS28 (HGNC:18178): (VPS28 subunit of ESCRT-I) This gene encodes a protein subunit of the ESCRT-I complex (endosomal complexes required for transport), which functions in the transport and sorting of proteins into subcellular vesicles. This complex can also be hijacked to facilitate the budding of enveloped viruses from the cell membrane. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Jul 2013]

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -3 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.48).
BP7
Synonymous conserved (PhyloP=1.05 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_013432.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.
GeneTranscriptTagsHGVScHGVSpEffectExon RankProteinUniProt
TONSL
NM_013432.5
MANE Select
c.4119C>Tp.Leu1373Leu
synonymous
Exon 26 of 26NP_038460.4

Ensembl Transcripts

Sel.
GeneTranscriptTagsHGVScHGVSpEffectExon RankProteinUniProt
TONSL
ENST00000409379.8
TSL:1 MANE Select
c.4119C>Tp.Leu1373Leu
synonymous
Exon 26 of 26ENSP00000386239.3Q96HA7-1
TONSL
ENST00000932056.1
c.4287C>Tp.Leu1429Leu
synonymous
Exon 27 of 27ENSP00000602115.1
TONSL
ENST00000971177.1
c.4149C>Tp.Leu1383Leu
synonymous
Exon 26 of 26ENSP00000641236.1

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
Data not reliable, filtered out with message: AC0
AF:
0.00
AC:
0
AN:
1378684
Hom.:
0
Cov.:
30
AF XY:
0.00
AC XY:
0
AN XY:
680214
African (AFR)
AF:
0.00
AC:
0
AN:
30618
American (AMR)
AF:
0.00
AC:
0
AN:
34776
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
24992
East Asian (EAS)
AF:
0.00
AC:
0
AN:
35172
South Asian (SAS)
AF:
0.00
AC:
0
AN:
78766
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
36292
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
4608
European-Non Finnish (NFE)
AF:
0.00
AC:
0
AN:
1075914
Other (OTH)
AF:
0.00
AC:
0
AN:
57546
GnomAD4 genome
Cov.:
33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.48
CADD
Benign
12
DANN
Benign
0.91
PhyloP100
1.0

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

Other links and lift over

dbSNP: rs1823055649; hg19: chr8-145654544; API