chr14-51094318-G-A
Variant summary
Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2
The NM_001387360.1(TRIM9):c.622C>T(p.Arg208Cys) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000291 in 1,613,526 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.000026 ( 0 hom., cov: 33)
Exomes 𝑓: 0.000029 ( 0 hom. )
Consequence
TRIM9
NM_001387360.1 missense
NM_001387360.1 missense
Scores
5
12
2
Clinical Significance
Conservation
PhyloP100: 7.88
Genes affected
TRIM9 (HGNC:16288): (tripartite motif containing 9) The protein encoded by this gene is a member of the tripartite motif (TRIM) family. The TRIM motif includes three zinc-binding domains, a RING, a B-box type 1 and a B-box type 2, and a coiled-coil region. The protein localizes to cytoplasmic bodies. Its function has not been identified. Alternate splicing of this gene generates two transcript variants encoding different isoforms. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -4 ACMG points.
BS2
?
High AC in GnomAdExome at 16 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TRIM9 | NM_001387360.1 | c.622C>T | p.Arg208Cys | missense_variant | 1/13 | ENST00000684578.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TRIM9 | ENST00000684578.1 | c.622C>T | p.Arg208Cys | missense_variant | 1/13 | NM_001387360.1 | |||
TRIM9 | ENST00000298355.7 | c.622C>T | p.Arg208Cys | missense_variant | 1/10 | 1 | P1 | ||
TRIM9 | ENST00000360392.4 | c.622C>T | p.Arg208Cys | missense_variant | 1/7 | 1 | |||
TRIM9 | ENST00000338969.9 | c.622C>T | p.Arg208Cys | missense_variant | 1/12 | 2 |
Frequencies
GnomAD3 genomes ? AF: 0.0000263 AC: 4AN: 152262Hom.: 0 Cov.: 33
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GnomAD3 exomes AF: 0.0000643 AC: 16AN: 248774Hom.: 0 AF XY: 0.0000964 AC XY: 13AN XY: 134872
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GnomAD4 exome AF: 0.0000294 AC: 43AN: 1461264Hom.: 0 Cov.: 31 AF XY: 0.0000316 AC XY: 23AN XY: 726928
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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 | Nov 10, 2022 | The c.622C>T (p.R208C) alteration is located in exon 1 (coding exon 1) of the TRIM9 gene. This alteration results from a C to T substitution at nucleotide position 622, causing the arginine (R) at amino acid position 208 to be replaced by a cysteine (C). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
BayesDel_addAF
Uncertain
D
BayesDel_noAF
Pathogenic
Cadd
Pathogenic
Dann
Pathogenic
DEOGEN2
Uncertain
T;.;.
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
LIST_S2
Pathogenic
D;D;D
M_CAP
Pathogenic
D
MetaRNN
Uncertain
D;D;D
MetaSVM
Uncertain
T
MutationAssessor
Uncertain
M;M;M
MutationTaster
Benign
D;D;D
PrimateAI
Pathogenic
D
PROVEAN
Uncertain
D;D;D
REVEL
Uncertain
Sift
Uncertain
D;D;D
Sift4G
Benign
T;T;T
Polyphen
D;D;D
Vest4
MVP
MPC
ClinPred
D
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