chr2-217804565-G-A
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Variant summary
Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2
The NM_001387777.1(TNS1):c.5414C>T(p.Thr1805Met) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00357 in 1,614,146 control chromosomes in the GnomAD database, including 14 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).
Frequency
Genomes: 𝑓 0.0024 ( 0 hom., cov: 31)
Exomes 𝑓: 0.0037 ( 14 hom. )
Consequence
TNS1
NM_001387777.1 missense
NM_001387777.1 missense
Scores
3
3
7
Clinical Significance
Conservation
PhyloP100: 9.78
Genes affected
TNS1 (HGNC:11973): (tensin 1) The protein encoded by this gene localizes to focal adhesions, regions of the plasma membrane where the cell attaches to the extracellular matrix. This protein crosslinks actin filaments and contains a Src homology 2 (SH2) domain, which is often found in molecules involved in signal transduction. This protein is a substrate of calpain II. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Apr 2015]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -10 ACMG points.
BP4
Computational evidence support a benign effect (MetaRNN=0.012797296).
BP6
Variant 2-217804565-G-A is Benign according to our data. Variant chr2-217804565-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 3033607.Status of the report is criteria_provided_single_submitter, 1 stars.
BS2
High AC in GnomAd4 at 363 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TNS1 | NM_001387777.1 | c.5414C>T | p.Thr1805Met | missense_variant | 33/33 | ENST00000682258.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TNS1 | ENST00000682258.1 | c.5414C>T | p.Thr1805Met | missense_variant | 33/33 | NM_001387777.1 | P2 |
Frequencies
GnomAD3 genomes AF: 0.00239 AC: 363AN: 152200Hom.: 0 Cov.: 31
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GnomAD3 exomes AF: 0.00252 AC: 630AN: 250420Hom.: 1 AF XY: 0.00256 AC XY: 347AN XY: 135400
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GnomAD4 exome AF: 0.00370 AC: 5406AN: 1461828Hom.: 14 Cov.: 31 AF XY: 0.00368 AC XY: 2673AN XY: 727228
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GnomAD4 genome AF: 0.00238 AC: 363AN: 152318Hom.: 0 Cov.: 31 AF XY: 0.00224 AC XY: 167AN XY: 74482
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ClinVar
Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
TNS1-related disorder Benign:1
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Jul 14, 2022 | This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Pathogenic
DANN
Pathogenic
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Uncertain
D
LIST_S2
Uncertain
D;D;D;D;D;.;D
M_CAP
Benign
D
MetaRNN
Benign
T;T;T;T;T;T;T
MetaSVM
Benign
T
MutationTaster
Benign
D;D;D
PrimateAI
Uncertain
T
Polyphen
1.0, 1.0
.;D;.;D;.;D;D
Vest4
0.45, 0.55, 0.46, 0.45, 0.44, 0.43
MVP
0.39
MPC
0.57
ClinPred
T
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
Varity_R
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Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at