6-133891777-G-A
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 0P and 0B.
The NM_003206.4(TCF21):c.515G>A(p.Arg172His) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000867 in 1,613,866 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.000013 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0000082 ( 0 hom. )
Consequence
TCF21
NM_003206.4 missense
NM_003206.4 missense
Scores
9
5
4
Clinical Significance
Conservation
PhyloP100: 7.94
Genes affected
TCF21 (HGNC:11632): (transcription factor 21) TCF21 encodes a transcription factor of the basic helix-loop-helix family. The TCF21 product is mesoderm specific, and expressed in embryonic epicardium, mesenchyme-derived tissues of lung, gut, gonad, and both mesenchymal and glomerular epithelial cells in the kidney. Two transcript variants encoding the same protein have been found for this gene. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 0 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TCF21 | NM_003206.4 | c.515G>A | p.Arg172His | missense_variant | 2/2 | ENST00000367882.5 | |
TCF21 | NM_198392.3 | c.515G>A | p.Arg172His | missense_variant | 2/3 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TCF21 | ENST00000367882.5 | c.515G>A | p.Arg172His | missense_variant | 2/2 | 1 | NM_003206.4 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000132 AC: 2AN: 152018Hom.: 0 Cov.: 32
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GnomAD4 exome AF: 0.00000821 AC: 12AN: 1461848Hom.: 0 Cov.: 34 AF XY: 0.00000963 AC XY: 7AN XY: 727232
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GnomAD4 genome ? AF: 0.0000132 AC: 2AN: 152018Hom.: 0 Cov.: 32 AF XY: 0.0000269 AC XY: 2AN XY: 74256
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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 | Dec 20, 2021 | The c.515G>A (p.R172H) alteration is located in exon 2 (coding exon 2) of the TCF21 gene. This alteration results from a G to A substitution at nucleotide position 515, causing the arginine (R) at amino acid position 172 to be replaced by a histidine (H). 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
Pathogenic
D
BayesDel_noAF
Pathogenic
Cadd
Pathogenic
Dann
Pathogenic
DEOGEN2
Uncertain
T;T
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Uncertain
D
M_CAP
Uncertain
D
MetaRNN
Uncertain
D;D
MetaSVM
Pathogenic
D
MutationAssessor
Benign
L;L
MutationTaster
Benign
D;D
PrimateAI
Uncertain
T
PROVEAN
Benign
N;N
REVEL
Pathogenic
Sift
Pathogenic
D;D
Sift4G
Pathogenic
D;D
Polyphen
D;D
Vest4
MutPred
Loss of MoRF binding (P = 0.0725);Loss of MoRF binding (P = 0.0725);
MVP
MPC
ClinPred
D
GERP RS
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