17-59028616-G-A
Variant summary
Our verdict is Pathogenic. Variant got 12 ACMG points: 12P and 0B. PVS1PM2PP5_Moderate
The NM_015294.6(TRIM37):c.2056C>T(p.Arg686Ter) variant causes a stop gained change. The variant allele was found at a frequency of 0.00000274 in 1,461,866 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 Pathogenic (★). Variant results in nonsense mediated mRNA decay.
Frequency
Genomes: not found (cov: 33)
Exomes 𝑓: 0.0000027 ( 0 hom. )
Consequence
TRIM37
NM_015294.6 stop_gained
NM_015294.6 stop_gained
Scores
3
3
1
Clinical Significance
Conservation
PhyloP100: 4.56
Genes affected
TRIM37 (HGNC:7523): (tripartite motif containing 37) This gene encodes a member of the tripartite motif (TRIM) family, whose members are involved in diverse cellular functions such as developmental patterning and oncogenesis. The TRIM motif includes zinc-binding domains, a RING finger region, a B-box motif and a coiled-coil domain. The RING finger and B-box domains chelate zinc and might be involved in protein-protein and/or protein-nucleic acid interactions. Mutations in this gene are associated with mulibrey (muscle-liver-brain-eye) nanism, an autosomal recessive disorder that involves several tissues of mesodermal origin. TRIM37 localizes in peroxisomal membranes, and has been implicated in human peroxisomal biogenesis disorders. [provided by RefSeq, Jul 2020]
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ACMG classification
Classification made for transcript
Verdict is Pathogenic. Variant got 12 ACMG points.
PVS1
?
Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
PM2
?
Very rare variant in population databases, with high coverage;
PP5
?
Variant 17-59028616-G-A is Pathogenic according to our data. Variant chr17-59028616-G-A is described in ClinVar as [Pathogenic]. Clinvar id is 56567.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr17-59028616-G-A is described in Lovd as [Pathogenic].
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TRIM37 | NM_015294.6 | c.2056C>T | p.Arg686Ter | stop_gained | 19/24 | ENST00000262294.12 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TRIM37 | ENST00000262294.12 | c.2056C>T | p.Arg686Ter | stop_gained | 19/24 | 1 | NM_015294.6 | P1 | |
TRIM37 | ENST00000393066.7 | c.2056C>T | p.Arg686Ter | stop_gained | 19/25 | 1 | P1 | ||
TRIM37 | ENST00000577554.5 | c.*1928C>T | 3_prime_UTR_variant, NMD_transcript_variant | 20/24 | 1 | ||||
TRIM37 | ENST00000393065.6 | c.1954C>T | p.Arg652Ter | stop_gained | 18/23 | 2 |
Frequencies
GnomAD3 genomes ? Cov.: 33
GnomAD3 genomes
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33
GnomAD3 exomes AF: 0.00000398 AC: 1AN: 251418Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 135886
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GnomAD4 exome AF: 0.00000274 AC: 4AN: 1461866Hom.: 0 Cov.: 31 AF XY: 0.00000413 AC XY: 3AN XY: 727228
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GnomAD4 genome ? Cov.: 33
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ClinVar
Significance: Pathogenic
Submissions summary: Pathogenic:2
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Mulibrey nanism syndrome Pathogenic:2
Likely pathogenic, no assertion criteria provided | literature only | Juha Muilu Group; Institute for Molecular Medicine Finland (FIMM) | - | - - |
Pathogenic, criteria provided, single submitter | clinical testing | Baylor Genetics | May 09, 2022 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
Cadd
Pathogenic
Dann
Uncertain
Eigen
Pathogenic
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
MutationTaster
Benign
A;A;A;A
Vest4
GERP RS
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