17-59049297-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_015294.6(TRIM37):​c.1411C>G​(p.Arg471Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000186 in 1,613,962 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: š‘“ 0.000013 ( 0 hom., cov: 32)
Exomes š‘“: 6.8e-7 ( 0 hom. )

Consequence

TRIM37
NM_015294.6 missense

Scores

1
5
13

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.74
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.2872157).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
TRIM37NM_015294.6 linkc.1411C>G p.Arg471Gly missense_variant Exon 15 of 24 ENST00000262294.12 NP_056109.1 O94972-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
TRIM37ENST00000262294.12 linkc.1411C>G p.Arg471Gly missense_variant Exon 15 of 24 1 NM_015294.6 ENSP00000262294.7 O94972-1

Frequencies

GnomAD3 genomes
AF:
0.0000131
AC:
2
AN:
152114
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0000483
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.00
GnomAD4 exome
AF:
6.84e-7
AC:
1
AN:
1461848
Hom.:
0
Cov.:
32
AF XY:
0.00
AC XY:
0
AN XY:
727224
show subpopulations
Gnomad4 AFR exome
AF:
0.0000299
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.0000131
AC:
2
AN:
152114
Hom.:
0
Cov.:
32
AF XY:
0.0000135
AC XY:
1
AN XY:
74298
show subpopulations
Gnomad4 AFR
AF:
0.0000483
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.0000151

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.13
BayesDel_addAF
Pathogenic
0.22
D
BayesDel_noAF
Uncertain
0.080
CADD
Benign
21
DANN
Uncertain
0.99
DEOGEN2
Benign
0.24
T;T;.
Eigen
Benign
-0.34
Eigen_PC
Benign
-0.32
FATHMM_MKL
Uncertain
0.81
D
LIST_S2
Uncertain
0.92
.;D;D
M_CAP
Benign
0.026
D
MetaRNN
Benign
0.29
T;T;T
MetaSVM
Benign
-0.65
T
MutationAssessor
Benign
1.1
L;L;.
PrimateAI
Benign
0.45
T
PROVEAN
Benign
-1.8
N;N;N
REVEL
Benign
0.23
Sift
Uncertain
0.0010
D;D;D
Sift4G
Benign
0.11
T;T;T
Polyphen
0.91
P;P;.
Vest4
0.57
MutPred
0.17
Gain of loop (P = 0.0045);Gain of loop (P = 0.0045);.;
MVP
0.38
MPC
0.29
ClinPred
0.74
D
GERP RS
0.30
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.1
Varity_R
0.28
gMVP
0.39

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.0
Details are displayed if max score is > 0.2

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs386834001; hg19: chr17-57126658; API