GeneBe

rs386834007

Variant names:

Variant summary

Our verdict is Pathogenic. The variant received 12 ACMG points: 12P and 0B. PVS1PM2PP5_Moderate

The NM_015294.6(TRIM37):​c.838_842delACTTT​(p.Thr280CysfsTer56) variant causes a frameshift change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000689 in 1,450,504 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: not found (cov: 32)
Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

TRIM37
NM_015294.6 frameshift

Scores

Not classified

Clinical Significance

Pathogenic criteria provided, single submitter P:3

Conservation

PhyloP100: 9.17

Publications

1 publications found
Variant links:
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]
TRIM37 Gene-Disease associations (from GenCC):
  • mulibrey nanism
    Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Orphanet, Labcorp Genetics (formerly Invitae), ClinGen, Ambry Genetics, G2P

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Pathogenic. The variant received 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 17-59064372-AAAAGT-A is Pathogenic according to our data. Variant chr17-59064372-AAAAGT-A is described in ClinVar as Pathogenic. ClinVar VariationId is 56572.Status of the report is criteria_provided_single_submitter, 1 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015294.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected
GeneTranscriptTagsHGVScHGVSpEffectExon RankProteinUniProt
TRIM37
NM_015294.6
MANE Select
c.838_842delACTTTp.Thr280CysfsTer56
frameshift
Exon 10 of 24NP_056109.1
TRIM37
NM_001353084.2
c.838_842delACTTTp.Thr280CysfsTer56
frameshift
Exon 10 of 24NP_001340013.1
TRIM37
NM_001005207.5
c.838_842delACTTTp.Thr280CysfsTer56
frameshift
Exon 10 of 25NP_001005207.1

Ensembl Transcripts

Selected
GeneTranscriptTagsHGVScHGVSpEffectExon RankProteinUniProt
TRIM37
ENST00000262294.12
TSL:1 MANE Select
c.838_842delACTTTp.Thr280CysfsTer56
frameshift
Exon 10 of 24ENSP00000262294.7
TRIM37
ENST00000393066.7
TSL:1
c.838_842delACTTTp.Thr280CysfsTer56
frameshift
Exon 10 of 25ENSP00000376785.3
TRIM37
ENST00000577554.5
TSL:1
n.*710_*714delACTTT
non_coding_transcript_exon
Exon 11 of 24ENSP00000462340.1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
AF:
6.89e-7
AC:
1
AN:
1450504
Hom.:
0
AF XY:
0.00
AC XY:
0
AN XY:
720752
show subpopulations
African (AFR)
AF:
0.00
AC:
0
AN:
33204
American (AMR)
AF:
0.00
AC:
0
AN:
43770
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
25714
East Asian (EAS)
AF:
0.00
AC:
0
AN:
39534
South Asian (SAS)
AF:
0.00
AC:
0
AN:
84428
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
52828
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
5516
European-Non Finnish (NFE)
AF:
9.04e-7
AC:
1
AN:
1105606
Other (OTH)
AF:
0.00
AC:
0
AN:
59904
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.425
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Exome Het
Variant carriers
0
2
4
6
8
10
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
GnomAD4 genome
Cov.:
32

ClinVar

ClinVar submissions as Germline

Significance:Pathogenic
Revision:criteria provided, single submitter
View on ClinVar
Pathogenic
VUS
Benign
Condition
3
-
-
Mulibrey nanism syndrome (3)

Computational scores

Source: dbNSFP v4.9

Name
Calibrated prediction
Score
Prediction
PhyloP100
9.2
Mutation Taster
=1/199
disease causing (ClinVar)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

Other links and lift over

dbSNP: rs386834007; hg19: chr17-57141733; API