rs386833416
Variant summary
Our verdict is Pathogenic. Variant got 12 ACMG points: 12P and 0B. PVS1PM2PP5_Moderate
The NM_015294.6(TRIM37):c.2212del(p.Glu738AsnfsTer31) variant causes a frameshift change. The variant allele was found at a frequency of 0.0000124 in 1,613,892 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Pathogenic (★). Variant results in nonsense mediated mRNA decay.
Frequency
Genomes: 𝑓 0.000033 ( 0 hom., cov: 33)
Exomes 𝑓: 0.000010 ( 0 hom. )
Consequence
TRIM37
NM_015294.6 frameshift
NM_015294.6 frameshift
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 5.75
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 17-59028459-TC-T is Pathogenic according to our data. Variant chr17-59028459-TC-T is described in ClinVar as [Pathogenic]. Clinvar id is 56568.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr17-59028459-TC-T is described in Lovd as [Pathogenic].
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TRIM37 | NM_015294.6 | c.2212del | p.Glu738AsnfsTer31 | frameshift_variant | 19/24 | ENST00000262294.12 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TRIM37 | ENST00000262294.12 | c.2212del | p.Glu738AsnfsTer31 | frameshift_variant | 19/24 | 1 | NM_015294.6 | P1 | |
TRIM37 | ENST00000393066.7 | c.2212del | p.Glu738AsnfsTer31 | frameshift_variant | 19/25 | 1 | P1 | ||
TRIM37 | ENST00000577554.5 | c.*2084del | 3_prime_UTR_variant, NMD_transcript_variant | 20/24 | 1 | ||||
TRIM37 | ENST00000393065.6 | c.2110del | p.Glu704AsnfsTer31 | frameshift_variant | 18/23 | 2 |
Frequencies
GnomAD3 genomes ? AF: 0.0000329 AC: 5AN: 152196Hom.: 0 Cov.: 33
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GnomAD3 exomes AF: 0.0000358 AC: 9AN: 251202Hom.: 0 AF XY: 0.0000368 AC XY: 5AN XY: 135812
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GnomAD4 exome AF: 0.0000103 AC: 15AN: 1461696Hom.: 0 Cov.: 31 AF XY: 0.0000138 AC XY: 10AN XY: 727162
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GnomAD4 genome ? AF: 0.0000329 AC: 5AN: 152196Hom.: 0 Cov.: 33 AF XY: 0.0000538 AC XY: 4AN XY: 74352
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ClinVar
Significance: Pathogenic
Submissions summary: Pathogenic:3
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Mulibrey nanism syndrome Pathogenic:2
Pathogenic, no assertion criteria provided | literature only | OMIM | Jul 01, 2000 | - - |
Pathogenic, no assertion criteria provided | literature only | Juha Muilu Group; Institute for Molecular Medicine Finland (FIMM) | - | - - |
not provided Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Invitae | Oct 08, 2023 | This sequence change creates a premature translational stop signal (p.Glu738Asnfs*31) in the TRIM37 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in TRIM37 are known to be pathogenic (PMID: 10888877, 15108285). This variant is present in population databases (rs386833416, gnomAD 0.03%). This premature translational stop signal has been observed in individual(s) with Mulabrey nanism (PMID: 10888877, 21865362). ClinVar contains an entry for this variant (Variation ID: 56568). For these reasons, this variant has been classified as Pathogenic. - |
Computational scores
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at