17-58998399-TG-T

Position:

• chr17-58998399-TG-T

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BS1_Supporting BS2

The NM_015294.6(TRIM37):​c.*977delC variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0022 in 985,434 control chromosomes in the GnomAD database, including 39 homozygotes. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.0091 (27 hom., cov: 33)
  • Exomes 𝑓: 0.00094 (12 hom.)
• Consequence: TRIM37 NM_015294.6 3_prime_UTR
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.641

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 (HGNC:):

ACMG classification

Verdict is Likely_benign. Variant got -5 ACMG points.

• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0091 (1387/152346) while in subpopulation AFR AF= 0.0307 (1277/41576). AF 95% confidence interval is 0.0293. There are 27 homozygotes in gnomad4. There are 674 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck. Existence of Clinvar submissions makes me limit the strength of this signal to Supporting
• BS2: High Homozygotes in GnomAd4 at 27 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TRIM37	NM_015294.6	c.*977delC		3_prime_UTR_variant	24/24	ENST00000262294.12	NP_056109.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TRIM37	ENST00000262294	c.*977delC		3_prime_UTR_variant	24/24	1	NM_015294.6	ENSP00000262294.7

Frequencies

GnomAD3 genomes AF: 0.00908 AC: 1382 AN: 152228 Hom.: 27 Cov.: 33

Gnomad AFR AF: 0.0307

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00549

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000176

Gnomad OTH AF: 0.00623

GnomAD4 exome AF: 0.000935 AC: 779 AN: 833088 Hom.: 12 Cov.: 29 AF XY: 0.000899 AC XY: 346 AN XY: 384702

Gnomad4 AFR exome AF: 0.0370

Gnomad4 AMR exome AF: 0.00203

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000122

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000161

Gnomad4 OTH exome AF: 0.00205

GnomAD4 genome AF: 0.00910 AC: 1387 AN: 152346 Hom.: 27 Cov.: 33 AF XY: 0.00905 AC XY: 674 AN XY: 74500

Gnomad4 AFR AF: 0.0307

Gnomad4 AMR AF: 0.00549

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000176

Gnomad4 OTH AF: 0.00616

Alfa AF: 0.00619 Hom.: 0

Bravo AF: 0.0105

Asia WGS AF: 0.00375 AC: 14 AN: 3478

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

Mulibrey nanism syndrome Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Computational scores

Source: dbNSFP v4.3

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

Other links and lift over

dbSNP: rs112918162; hg19: chr17-57075760;