17-78049969-C-T
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_001142640.2(TNRC6C):c.1537C>T(p.Pro513Ser) variant causes a missense change. The variant allele was found at a frequency of 0.0000589 in 1,613,936 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.000039 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000061 ( 0 hom. )
Consequence
TNRC6C
NM_001142640.2 missense
NM_001142640.2 missense
Scores
4
10
Clinical Significance
Conservation
PhyloP100: 5.14
Genes affected
TNRC6C (HGNC:29318): (trinucleotide repeat containing adaptor 6C) Predicted to enable RNA binding activity. Involved in gene silencing by miRNA; positive regulation of nuclear-transcribed mRNA catabolic process, deadenylation-dependent decay; and positive regulation of nuclear-transcribed mRNA poly(A) tail shortening. Predicted to be located in cytosol. Predicted to be active in P-body and nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 0 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
BP4
?
Computational evidence support a benign effect (MetaRNN=0.15018952).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TNRC6C | NM_001142640.2 | c.1537C>T | p.Pro513Ser | missense_variant | 5/23 | ENST00000696270.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TNRC6C | ENST00000696270.1 | c.1537C>T | p.Pro513Ser | missense_variant | 5/23 | NM_001142640.2 | P4 |
Frequencies
GnomAD3 genomes ? AF: 0.0000394 AC: 6AN: 152242Hom.: 0 Cov.: 32
GnomAD3 genomes
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GnomAD3 exomes AF: 0.0000723 AC: 18AN: 248972Hom.: 0 AF XY: 0.0000888 AC XY: 12AN XY: 135178
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GnomAD4 exome AF: 0.0000609 AC: 89AN: 1461694Hom.: 0 Cov.: 33 AF XY: 0.0000646 AC XY: 47AN XY: 727128
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GnomAD4 genome ? AF: 0.0000394 AC: 6AN: 152242Hom.: 0 Cov.: 32 AF XY: 0.0000269 AC XY: 2AN XY: 74382
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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 03, 2021 | The c.907C>T (p.P303S) alteration is located in exon 4 (coding exon 1) of the TNRC6C gene. This alteration results from a C to T substitution at nucleotide position 907, causing the proline (P) at amino acid position 303 to be replaced by a serine (S). 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
Benign
Cadd
Uncertain
Dann
Benign
DEOGEN2
Benign
T;.;T;T;.
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
LIST_S2
Uncertain
D;.;.;D;D
M_CAP
Benign
T
MetaRNN
Benign
T;T;T;T;T
MetaSVM
Benign
T
MutationTaster
Benign
D;D;D;D;D;D
PrimateAI
Benign
T
Polyphen
0.98, 1.0
.;D;D;D;D
Vest4
0.48, 0.47, 0.54, 0.48
MVP
0.24
MPC
0.97
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