chr3-49412633-C-A
Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4
The NM_022171.3(TCTA):c.207C>A(p.His69Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000161 in 1,613,892 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.00012 ( 0 hom., cov: 34)
Exomes 𝑓: 0.0000048 ( 0 hom. )
Consequence
TCTA
NM_022171.3 missense
NM_022171.3 missense
Scores
1
7
11
Clinical Significance
Conservation
PhyloP100: 2.14
Genes affected
TCTA (HGNC:11692): (T cell leukemia translocation altered) Involved in negative regulation of osteoclast differentiation and osteoclast fusion. Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]
RHOA (HGNC:667): (ras homolog family member A) This gene encodes a member of the Rho family of small GTPases, which cycle between inactive GDP-bound and active GTP-bound states and function as molecular switches in signal transduction cascades. Rho proteins promote reorganization of the actin cytoskeleton and regulate cell shape, attachment, and motility. Overexpression of this gene is associated with tumor cell proliferation and metastasis. Multiple alternatively spliced variants have been identified. [provided by RefSeq, Sep 2015]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 1 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
BP4
?
Computational evidence support a benign effect (MetaRNN=0.36453107).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TCTA | NM_022171.3 | c.207C>A | p.His69Gln | missense_variant | 1/3 | ENST00000273590.4 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TCTA | ENST00000273590.4 | c.207C>A | p.His69Gln | missense_variant | 1/3 | 1 | NM_022171.3 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.000125 AC: 19AN: 152238Hom.: 0 Cov.: 34
GnomAD3 genomes
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GnomAD3 exomes AF: 0.0000239 AC: 6AN: 251232Hom.: 0 AF XY: 0.0000147 AC XY: 2AN XY: 135814
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GnomAD4 exome AF: 0.00000479 AC: 7AN: 1461536Hom.: 0 Cov.: 32 AF XY: 0.00000413 AC XY: 3AN XY: 727012
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GnomAD4 genome ? AF: 0.000125 AC: 19AN: 152356Hom.: 0 Cov.: 34 AF XY: 0.000148 AC XY: 11AN XY: 74498
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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 submitter | clinical testing | Ambry Genetics | Nov 15, 2023 | The c.207C>A (p.H69Q) alteration is located in exon 1 (coding exon 1) of the TCTA gene. This alteration results from a C to A substitution at nucleotide position 207, causing the histidine (H) at amino acid position 69 to be replaced by a glutamine (Q). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Uncertain
Cadd
Uncertain
Dann
Uncertain
DEOGEN2
Benign
T
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Benign
N
LIST_S2
Benign
T
M_CAP
Benign
T
MetaRNN
Benign
T
MetaSVM
Benign
T
MutationAssessor
Benign
N
MutationTaster
Benign
D
PrimateAI
Uncertain
T
PROVEAN
Pathogenic
D
REVEL
Benign
Sift
Uncertain
D
Sift4G
Uncertain
D
Polyphen
D
Vest4
MutPred
Loss of sheet (P = 0.0315);
MVP
MPC
ClinPred
D
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
Varity_R
gMVP
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