rs12677973

Variant summary

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

The NM_013432.5(TONSL):​c.861G>T​(p.Gln287His) variant causes a missense 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. 9/14 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 34)

Consequence

TONSL
NM_013432.5 missense

Scores

3
8

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.428
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]

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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=0.16857606).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
TONSLNM_013432.5 linkuse as main transcriptc.861G>T p.Gln287His missense_variant 7/26 ENST00000409379.8
TONSLXM_011517050.3 linkuse as main transcriptc.861G>T p.Gln287His missense_variant 7/19
TONSLXM_011517048.3 linkuse as main transcriptc.-2G>T 5_prime_UTR_variant 1/19
TONSLXM_011517049.3 linkuse as main transcriptc.-2G>T 5_prime_UTR_variant 1/19

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
TONSLENST00000409379.8 linkuse as main transcriptc.861G>T p.Gln287His missense_variant 7/261 NM_013432.5 P1Q96HA7-1
TONSLENST00000497613.2 linkuse as main transcriptn.816G>T non_coding_transcript_exon_variant 1/172

Frequencies

GnomAD3 genomes
Cov.:
34
GnomAD4 exome
Cov.:
34
GnomAD4 genome
Cov.:
34

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.20
BayesDel_addAF
Uncertain
0.054
T
BayesDel_noAF
Benign
-0.43
CADD
Benign
16
DANN
Uncertain
0.98
Eigen
Benign
-0.27
Eigen_PC
Benign
-0.24
FATHMM_MKL
Uncertain
0.89
D
M_CAP
Benign
0.012
T
MetaRNN
Benign
0.17
T
MutationTaster
Benign
0.99
N
Sift4G
Benign
0.20
T
Vest4
0.083
MVP
0.55
ClinPred
0.69
D
GERP RS
1.6
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7

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.

Other links and lift over

dbSNP: rs12677973; hg19: chr8-145667424; API