chr22-40261955-C-T
Variant summary
Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4BS1_SupportingBS2
The NM_001162501.2(TNRC6B):c.239C>T(p.Pro80Leu) variant causes a missense change. The variant allele was found at a frequency of 0.000018 in 1,612,728 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 0.000033 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000016 ( 0 hom. )
Consequence
TNRC6B
NM_001162501.2 missense
NM_001162501.2 missense
Scores
1
7
9
Clinical Significance
Conservation
PhyloP100: 4.56
Genes affected
TNRC6B (HGNC:29190): (trinucleotide repeat containing adaptor 6B) Enables RNA binding activity. Involved in regulation of gene expression. Predicted to be located in cytosol. Predicted to be active in P-body and nucleoplasm. Implicated in subserous uterine fibroid and uterine fibroid. [provided by Alliance of Genome Resources, Apr 2022]
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ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -6 ACMG points.
BP4
?
Computational evidence support a benign effect (MetaRNN=0.27443457).
BS1
?
Variant frequency is greater than expected in population eas. gnomad4 allele frequency = 0.0000328 (5/152302) while in subpopulation EAS AF= 0.000579 (3/5180). AF 95% confidence interval is 0.000157. There are 0 homozygotes in gnomad4. There are 2 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck. Existence of Clinvar submissions makes me limit the strength of this signal to Supporting
BS2
?
High AC in GnomAd at 5 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TNRC6B | NM_001162501.2 | c.239C>T | p.Pro80Leu | missense_variant | 4/23 | ENST00000454349.7 | |
LOC124905121 | XR_007068107.1 | n.304-1587G>A | intron_variant, non_coding_transcript_variant | ||||
TNRC6B | NM_015088.3 | c.239C>T | p.Pro80Leu | missense_variant | 4/21 | ||
TNRC6B | NM_001024843.2 | c.347C>T | p.Pro116Leu | missense_variant | 7/24 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TNRC6B | ENST00000454349.7 | c.239C>T | p.Pro80Leu | missense_variant | 4/23 | 2 | NM_001162501.2 | P3 | |
TNRC6B | ENST00000335727.13 | c.239C>T | p.Pro80Leu | missense_variant | 4/21 | 1 | |||
TNRC6B | ENST00000402203.5 | c.347C>T | p.Pro116Leu | missense_variant | 7/24 | 1 | A2 | ||
TNRC6B | ENST00000301923.13 | c.347C>T | p.Pro116Leu | missense_variant | 7/24 | 5 | A2 |
Frequencies
GnomAD3 genomes ? AF: 0.0000329 AC: 5AN: 152186Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.00000813 AC: 2AN: 245990Hom.: 0 AF XY: 0.00000746 AC XY: 1AN XY: 134050
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GnomAD4 exome AF: 0.0000164 AC: 24AN: 1460426Hom.: 0 Cov.: 30 AF XY: 0.0000193 AC XY: 14AN XY: 726408
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Sep 01, 2022 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
Cadd
Pathogenic
Dann
Uncertain
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
LIST_S2
Pathogenic
D;.;D;D
M_CAP
Benign
T
MetaRNN
Benign
T;T;T;T
MetaSVM
Benign
T
MutationTaster
Benign
D;D;D;D
PrimateAI
Uncertain
T
PROVEAN
Uncertain
D;D;D;D
REVEL
Benign
Sift
Benign
D;D;D;D
Sift4G
Uncertain
D;D;D;D
Polyphen
D;D;D;D
Vest4
MVP
MPC
0.64
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