2-121757240-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The ENST00000389682.8(TSN):​c.67G>A​(p.Glu23Lys) variant causes a missense, splice region change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 2/3 splice prediction tools predicting alterations to normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Consequence

TSN
ENST00000389682.8 missense, splice_region

Scores

3
5
11
Splicing: ADA: 0.9779
2

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.28
Variant links:
Genes affected
TSN (HGNC:12379): (translin) This gene encodes a DNA-binding protein which specifically recognizes conserved target sequences at the breakpoint junction of chromosomal translocations. Translin polypeptides form a multimeric structure that is responsible for its DNA-binding activity. Recombination-associated motifs and translin-binding sites are present at recombination hotspots and may serve as indicators of breakpoints in genes which are fused by translocations. These binding activities may play a crucial role in chromosomal translocation in lymphoid neoplasms. This protein encoded by this gene, when complexed with translin-associated protein X, also forms a Mg ion-dependent endoribonuclease that promotes RNA-induced silencing complex (RISC) activation. Alternative splicing results in multiple transcript variants. [provided by RefSeq, May 2012]

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
TSNNM_004622.3 linkuse as main transcriptc.67G>A p.Glu23Lys missense_variant, splice_region_variant 2/6 ENST00000389682.8 NP_004613.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
TSNENST00000389682.8 linkuse as main transcriptc.67G>A p.Glu23Lys missense_variant, splice_region_variant 2/61 NM_004622.3 ENSP00000374332 P1Q15631-1

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
Cov.:
30
GnomAD4 genome
Cov.:
33

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 submitterclinical testingAmbry GeneticsAug 08, 2023The c.67G>A (p.E23K) alteration is located in exon 2 (coding exon 2) of the TSN gene. This alteration results from a G to A substitution at nucleotide position 67, causing the glutamic acid (E) at amino acid position 23 to be replaced by a lysine (K). 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
Pathogenic
0.88
BayesDel_addAF
Uncertain
0.051
T
BayesDel_noAF
Benign
-0.16
CADD
Pathogenic
27
DANN
Uncertain
1.0
DEOGEN2
Benign
0.32
T;.;T
Eigen
Uncertain
0.22
Eigen_PC
Uncertain
0.30
FATHMM_MKL
Uncertain
0.96
D
LIST_S2
Pathogenic
0.98
D;D;D
M_CAP
Benign
0.013
T
MetaRNN
Benign
0.26
T;T;T
MetaSVM
Benign
-0.80
T
MutationAssessor
Benign
1.6
L;L;.
MutationTaster
Benign
1.0
D;D;D
PrimateAI
Pathogenic
0.86
D
PROVEAN
Benign
-2.1
N;D;N
REVEL
Benign
0.16
Sift
Benign
0.23
T;T;T
Sift4G
Benign
0.30
T;D;T
Polyphen
0.0010
B;.;.
Vest4
0.38
MutPred
0.62
Gain of MoRF binding (P = 0.0055);Gain of MoRF binding (P = 0.0055);.;
MVP
0.10
MPC
1.2
ClinPred
0.95
D
GERP RS
4.4
Varity_R
0.47
gMVP
0.44

Splicing

Name
Calibrated prediction
Score
Prediction
dbscSNV1_ADA
Pathogenic
0.98
dbscSNV1_RF
Pathogenic
0.83
SpliceAI score (max)
0.050
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr2-122514816; API