22-40251193-A-C
Variant summary
Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4BP6_ModerateBS1BS2
The NM_001162501.2(TNRC6B):c.108A>C(p.Lys36Asn) variant causes a missense change. The variant allele was found at a frequency of 0.000383 in 1,535,714 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 Likely benign (★).
Frequency
Genomes: 𝑓 0.00021 ( 0 hom., cov: 31)
Exomes 𝑓: 0.00040 ( 0 hom. )
Consequence
TNRC6B
NM_001162501.2 missense
NM_001162501.2 missense
Scores
3
5
9
Clinical Significance
Conservation
PhyloP100: 6.21
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 Benign. Variant got -11 ACMG points.
BP4
?
Computational evidence support a benign effect (MetaRNN=0.28448594).
BP6
?
Variant 22-40251193-A-C is Benign according to our data. Variant chr22-40251193-A-C is described in ClinVar as [Likely_benign]. Clinvar id is 3026122.Status of the report is criteria_provided_single_submitter, 1 stars.
BS1
?
Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00021 (32/152172) while in subpopulation NFE AF= 0.000294 (20/68042). AF 95% confidence interval is 0.000194. There are 0 homozygotes in gnomad4. There are 10 alleles in male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck.
BS2
?
High AC in GnomAd at 32 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TNRC6B | NM_001162501.2 | c.108A>C | p.Lys36Asn | missense_variant | 3/23 | ENST00000454349.7 | |
TNRC6B | NM_015088.3 | c.108A>C | p.Lys36Asn | missense_variant | 3/21 | ||
TNRC6B | NM_001024843.2 | c.216A>C | p.Lys72Asn | missense_variant | 6/24 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TNRC6B | ENST00000454349.7 | c.108A>C | p.Lys36Asn | missense_variant | 3/23 | 2 | NM_001162501.2 | P3 | |
TNRC6B | ENST00000335727.13 | c.108A>C | p.Lys36Asn | missense_variant | 3/21 | 1 | |||
TNRC6B | ENST00000402203.5 | c.216A>C | p.Lys72Asn | missense_variant | 6/24 | 1 | A2 | ||
TNRC6B | ENST00000301923.13 | c.216A>C | p.Lys72Asn | missense_variant | 6/24 | 5 | A2 |
Frequencies
GnomAD3 genomes ? AF: 0.000210 AC: 32AN: 152172Hom.: 0 Cov.: 31
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GnomAD3 exomes AF: 0.000121 AC: 18AN: 148536Hom.: 0 AF XY: 0.000101 AC XY: 8AN XY: 79084
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GnomAD4 exome AF: 0.000402 AC: 556AN: 1383542Hom.: 0 Cov.: 28 AF XY: 0.000357 AC XY: 244AN XY: 682714
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ClinVar
Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Dec 01, 2023 | TNRC6B: BS1 - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
Cadd
Uncertain
Dann
Uncertain
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
MetaSVM
Benign
T
MutationTaster
Benign
D;D;N;N
PrimateAI
Pathogenic
D
PROVEAN
Benign
N;N;N;N
REVEL
Benign
Sift
Pathogenic
D;D;D;D
Sift4G
Benign
T;T;D;D
Polyphen
D;D;D;D
Vest4
MutPred
0.30
.;.;Loss of methylation at K36 (P = 7e-04);Loss of methylation at K36 (P = 7e-04);
MVP
MPC
0.17
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