11-5611163-C-T
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Variant summary
Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3
The NM_001003818.3(TRIM6):c.1372C>T(p.Pro458Ser) variant causes a missense change. The variant allele was found at a frequency of 0.000075 in 1,614,192 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.000053 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000077 ( 0 hom. )
Consequence
TRIM6
NM_001003818.3 missense
NM_001003818.3 missense
Scores
5
9
4
Clinical Significance
Conservation
PhyloP100: 4.49
Genes affected
TRIM6 (HGNC:16277): (tripartite motif containing 6) 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, B-box type 1 and B-box type 2 domain, and a coiled-coil region. The protein localizes to the nucleus, but its specific function has not been identified. This gene is mapped to chromosome 11p15, where it resides within a TRIM gene cluster. Alternative splicing results in multiple transcript variants. A read-through transcript from this gene into the downstream TRIM34 gene has also been observed, which results in a fusion product from these neighboring family members. [provided by RefSeq, Oct 2010]
TRIM6-TRIM34 (HGNC:33440): (TRIM6-TRIM34 readthrough) 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. This gene represents a readthrough transcript from genes TRIM6 and TRIM34, and it was described as a splice variant of TRIM34. This gene is mapped to chromosome 11p15, where it resides within a TRIM gene cluster. [provided by RefSeq, Nov 2009]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 3 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.764
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
TRIM6 | NM_001003818.3 | c.1372C>T | p.Pro458Ser | missense_variant | 8/8 | ENST00000380097.8 | NP_001003818.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
TRIM6 | ENST00000380097.8 | c.1372C>T | p.Pro458Ser | missense_variant | 8/8 | 1 | NM_001003818.3 | ENSP00000369440.3 | ||
TRIM6-TRIM34 | ENST00000354852.5 | c.985+602C>T | intron_variant | 2 | ENSP00000346916.5 | |||||
ENSG00000239920 | ENST00000380259.7 | n.*421+15438G>A | intron_variant | 5 | ENSP00000369609.3 |
Frequencies
GnomAD3 genomes AF: 0.0000526 AC: 8AN: 152182Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.0000477 AC: 12AN: 251484Hom.: 0 AF XY: 0.0000515 AC XY: 7AN XY: 135918
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GnomAD4 exome AF: 0.0000773 AC: 113AN: 1461892Hom.: 0 Cov.: 34 AF XY: 0.0000646 AC XY: 47AN XY: 727248
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GnomAD4 genome AF: 0.0000525 AC: 8AN: 152300Hom.: 0 Cov.: 32 AF XY: 0.0000537 AC XY: 4AN XY: 74464
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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 | Mar 12, 2024 | The c.1372C>T (p.P458S) alteration is located in exon 8 (coding exon 8) of the TRIM6 gene. This alteration results from a C to T substitution at nucleotide position 1372, causing the proline (P) at amino acid position 458 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
Pathogenic
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Uncertain
DANN
Uncertain
DEOGEN2
Benign
T;.;.;.;.;.;.;.
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Pathogenic
D
LIST_S2
Uncertain
D;.;.;D;.;.;D;D
M_CAP
Pathogenic
D
MetaRNN
Pathogenic
D;D;D;D;D;D;D;D
MetaSVM
Uncertain
D
MutationAssessor
Uncertain
M;.;.;.;.;.;.;.
PROVEAN
Pathogenic
D;D;D;D;D;D;D;.
REVEL
Uncertain
Sift
Uncertain
D;D;D;D;D;D;D;.
Sift4G
Uncertain
D;D;D;D;D;D;D;D
Polyphen
D;.;D;D;.;.;.;D
Vest4
MVP
MPC
0.22
ClinPred
D
GERP RS
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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