chr16-24789277-G-A
Variant summary
Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2
The NM_014494.4(TNRC6A):c.635G>A(p.Arg212Gln) variant causes a missense change. The variant allele was found at a frequency of 0.0000143 in 1,612,120 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.000026 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000013 ( 0 hom. )
Consequence
TNRC6A
NM_014494.4 missense
NM_014494.4 missense
Scores
1
2
15
Clinical Significance
Conservation
PhyloP100: 3.95
Genes affected
TNRC6A (HGNC:11969): (trinucleotide repeat containing adaptor 6A) This gene encodes a member of the trinucleotide repeat containing 6 protein family. The protein functions in post-transcriptional gene silencing through the RNA interference (RNAi) and microRNA pathways. The protein associates with messenger RNAs and Argonaute proteins in cytoplasmic bodies known as GW-bodies or P-bodies. Inhibiting expression of this gene delocalizes other GW-body proteins and impairs RNAi and microRNA-induced gene silencing. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -8 ACMG points.
BP4
?
Computational evidence support a benign effect (MetaRNN=0.059803337).
BS2
?
High AC in GnomAdExome at 7 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TNRC6A | NM_014494.4 | c.635G>A | p.Arg212Gln | missense_variant | 6/25 | ENST00000395799.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TNRC6A | ENST00000395799.8 | c.635G>A | p.Arg212Gln | missense_variant | 6/25 | 5 | NM_014494.4 | A2 | |
TNRC6A | ENST00000491718.5 | c.*160G>A | 3_prime_UTR_variant, NMD_transcript_variant | 3/22 | 1 | ||||
TNRC6A | ENST00000315183.11 | c.635G>A | p.Arg212Gln | missense_variant | 6/24 | 5 | P4 |
Frequencies
GnomAD3 genomes ? AF: 0.0000263 AC: 4AN: 152120Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.0000282 AC: 7AN: 248522Hom.: 0 AF XY: 0.0000148 AC XY: 2AN XY: 134716
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GnomAD4 exome AF: 0.0000130 AC: 19AN: 1460000Hom.: 0 Cov.: 30 AF XY: 0.00000689 AC XY: 5AN XY: 726138
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GnomAD4 genome ? AF: 0.0000263 AC: 4AN: 152120Hom.: 0 Cov.: 32 AF XY: 0.0000269 AC XY: 2AN XY: 74290
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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 | Apr 22, 2022 | The c.635G>A (p.R212Q) alteration is located in exon 6 (coding exon 6) of the TNRC6A gene. This alteration results from a G to A substitution at nucleotide position 635, causing the arginine (R) at amino acid position 212 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
Benign
Cadd
Benign
Dann
Uncertain
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Pathogenic
D
LIST_S2
Uncertain
D;D
M_CAP
Benign
T
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
0.0
.;B
Vest4
MutPred
Loss of phosphorylation at S210 (P = 0.1139);Loss of phosphorylation at S210 (P = 0.1139);
MVP
MPC
0.10
ClinPred
T
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