rs61758100

Positions:

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The ENST00000262294.12(TRIM37):c.398C>T(p.Ala133Val) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00808 in 1,613,754 control chromosomes in the GnomAD database, including 73 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A133G) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.0064 ( 4 hom., cov: 32)

Exomes 𝑓: 0.0083 ( 69 hom. )

Consequence

TRIM37
ENST00000262294.12 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:9

Conservation

PhyloP100: 7.67

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.008718789).

BP6

Variant 17-59081191-G-A is Benign according to our data. Variant chr17-59081191-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 198216.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-59081191-G-A is described in Lovd as [Likely_benign]. Variant chr17-59081191-G-A is described in Lovd as [Benign].

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0064 (974/152202) while in subpopulation NFE AF= 0.011 (750/68020). AF 95% confidence interval is 0.0104. There are 4 homozygotes in gnomad4. There are 497 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 4 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TRIM37	NM_015294.6 linkuse as main transcript	c.398C>T	p.Ala133Val	missense_variant	6/24	ENST00000262294.12	NP_056109.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TRIM37	ENST00000262294.12 linkuse as main transcript	c.398C>T	p.Ala133Val	missense_variant	6/24	1	NM_015294.6	ENSP00000262294	P1	O94972-1

Frequencies

GnomAD3 genomes

AF:

0.00640

AC:

974

AN:

152084

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00130

Gnomad AMI

AF:

0.0132

Gnomad AMR

AF:

0.00203

Gnomad ASJ

AF:

0.00202

Gnomad EAS

AF:

0.000192

Gnomad SAS

AF:

0.000622

Gnomad FIN

AF:

0.0104

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0110

Gnomad OTH

AF:

0.00287

GnomAD3 exomes

AF:

0.00630

AC:

1583

AN:

251448

Hom.:

AF XY:

0.00630

AC XY:

856

AN XY:

135892

show subpopulations

Gnomad AFR exome

AF:

0.00135

Gnomad AMR exome

AF:

0.00182

Gnomad ASJ exome

AF:

0.000794

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000751

Gnomad FIN exome

AF:

0.0129

Gnomad NFE exome

AF:

0.0101

Gnomad OTH exome

AF:

0.00717

GnomAD4 exome

AF:

0.00825

AC:

12061

AN:

1461552

Hom.:

Cov.:

AF XY:

0.00806

AC XY:

5860

AN XY:

727096

show subpopulations

Gnomad4 AFR exome

AF:

0.000896

Gnomad4 AMR exome

AF:

0.00161

Gnomad4 ASJ exome

AF:

0.00142

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.000939

Gnomad4 FIN exome

AF:

0.0130

Gnomad4 NFE exome

AF:

0.00972

Gnomad4 OTH exome

AF:

0.00553

GnomAD4 genome

AF:

0.00640

AC:

974

AN:

152202

Hom.:

Cov.:

AF XY:

0.00668

AC XY:

497

AN XY:

74404

show subpopulations

Gnomad4 AFR

AF:

0.00130

Gnomad4 AMR

AF:

0.00203

Gnomad4 ASJ

AF:

0.00202

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.000623

Gnomad4 FIN

AF:

0.0104

Gnomad4 NFE

AF:

0.0110

Gnomad4 OTH

AF:

0.00284

Alfa

AF:

0.00860

Hom.:

Bravo

AF:

0.00519

TwinsUK

AF:

0.00701

AC:

ALSPAC

AF:

0.00830

AC:

ESP6500AA

AF:

0.00250

AC:

ESP6500EA

AF:

0.00919

AC:

ExAC

AF:

0.00692

AC:

840

Asia WGS

AF:

0.000578

AC:

AN:

3476

EpiCase

AF:

0.00834

EpiControl

AF:

0.00717

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:9

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:6

Benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Mar 01, 2024	TRIM37: BS1, BS2 -
Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Likely benign, no assertion criteria provided	clinical testing	Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC)	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 31, 2024	- -
Likely benign, criteria provided, single submitter	clinical testing	Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics	Aug 24, 2017	- -
Likely benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 15, 2018	- -

not specified

Benign:2

Benign, no assertion criteria provided	clinical testing	Genome Diagnostics Laboratory, Amsterdam University Medical Center	-	- -
Benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Jun 16, 2014	- -

Mulibrey nanism syndrome

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Apr 27, 2017

This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases was too high to be consistent with this variant causing disease. Therefore, this variant is classified as benign. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.23

BayesDel_addAF

Benign

-0.43

BayesDel_noAF

Benign

-0.38

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.12

T;T;.

Eigen

Benign

0.064

Eigen_PC

Uncertain

0.29

FATHMM_MKL

Uncertain

0.95

LIST_S2

Uncertain

0.95

.;D;D

MetaRNN

Benign

0.0087

T;T;T

MetaSVM

Benign

-0.96

MutationAssessor

Benign

0.0

N;N;.

MutationTaster

Benign

1.0

D;D;D;D

PrimateAI

Uncertain

0.68

PROVEAN

Benign

-1.1

N;N;N

REVEL

Benign

0.057

Sift

Benign

0.090

T;T;T

Sift4G

Benign

0.088

T;T;T

Polyphen

0.057

B;B;.

Vest4

0.30

MVP

0.41

MPC

0.72

ClinPred

0.016

GERP RS

5.6

Varity_R

0.17

gMVP

0.57

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over