17-59070887-G-C

Variant names:

• chr17-59070887-G-C
• rs386834005
• NM_015294.6:c.745C>G

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_015294.6(TRIM37):​c.745C>G​(p.Gln249Glu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: TRIM37 NM_015294.6 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 10.0
• Publications: 0 publications found

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, G2P, Labcorp Genetics (formerly Invitae), ClinGen, Ambry Genetics

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.4144327).

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TRIM37	NM_015294.6	MANE Select	c.745C>G	p.Gln249Glu	missense	Exon 9 of 24	NP_056109.1	O94972-1
	TRIM37	NM_001353084.2		c.745C>G	p.Gln249Glu	missense	Exon 9 of 24	NP_001340013.1
	TRIM37	NM_001005207.5		c.745C>G	p.Gln249Glu	missense	Exon 9 of 25	NP_001005207.1	O94972-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TRIM37	ENST00000262294.12	TSL:1 MANE Select	c.745C>G	p.Gln249Glu	missense	Exon 9 of 24	ENSP00000262294.7	O94972-1
	TRIM37	ENST00000393066.7	TSL:1	c.745C>G	p.Gln249Glu	missense	Exon 9 of 25	ENSP00000376785.3	O94972-1
	TRIM37	ENST00000577554.5	TSL:1	n.*617C>G		non_coding_transcript_exon	Exon 10 of 24	ENSP00000462340.1	J3KS72

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.28
PhyloP100		10
Varity_R		0.25
gMVP		0.58

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		Details are displayed if max score is > 0.2

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs386834005; hg19: chr17-57148248;