6-133889491-G-C
Variant summary
Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2
The NM_003206.4(TCF21):c.94G>C(p.Val32Leu) variant causes a missense change. The variant allele was found at a frequency of 0.0000911 in 1,614,150 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).
Frequency
Genomes: 𝑓 0.00014 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000086 ( 1 hom. )
Consequence
TCF21
NM_003206.4 missense
NM_003206.4 missense
Scores
1
17
Clinical Significance
Conservation
PhyloP100: 5.20
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 Benign. Variant got -10 ACMG points.
BP4
?
Computational evidence support a benign effect (MetaRNN=0.006390035).
BP6
?
Variant 6-133889491-G-C is Benign according to our data. Variant chr6-133889491-G-C is described in ClinVar as [Likely_benign]. Clinvar id is 3039740.Status of the report is criteria_provided_single_submitter, 1 stars.
BS2
?
High AC in GnomAd at 22 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TCF21 | NM_003206.4 | c.94G>C | p.Val32Leu | missense_variant | 1/2 | ENST00000367882.5 | |
TCF21 | NM_198392.3 | c.94G>C | p.Val32Leu | missense_variant | 1/3 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TCF21 | ENST00000367882.5 | c.94G>C | p.Val32Leu | missense_variant | 1/2 | 1 | NM_003206.4 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.000145 AC: 22AN: 152146Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.000429 AC: 108AN: 251458Hom.: 1 AF XY: 0.000434 AC XY: 59AN XY: 135902
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GnomAD4 exome AF: 0.0000855 AC: 125AN: 1461886Hom.: 1 Cov.: 34 AF XY: 0.0000935 AC XY: 68AN XY: 727244
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GnomAD4 genome ? AF: 0.000144 AC: 22AN: 152264Hom.: 0 Cov.: 32 AF XY: 0.000188 AC XY: 14AN XY: 74462
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ClinVar
Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
TCF21-related disorder Benign:1
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Sep 17, 2019 | 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
Benign
Dann
Benign
DEOGEN2
Benign
T;T
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Uncertain
D
M_CAP
Benign
D
MetaRNN
Benign
T;T
MetaSVM
Benign
T
MutationAssessor
Benign
N;N
MutationTaster
Benign
N;N
PrimateAI
Benign
T
PROVEAN
Benign
N;N
REVEL
Benign
Sift
Benign
T;T
Sift4G
Benign
T;T
Polyphen
B;B
Vest4
MVP
MPC
ClinPred
T
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