17-58998743-T-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_015294.6(TRIM37):c.*634A>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.366 in 985,222 control chromosomes in the GnomAD database, including 66,148 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.34 (9175 hom., cov: 33)
  • Exomes 𝑓: 0.37 (56973 hom.)
• Consequence: TRIM37 NM_015294.6 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.0480

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]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BP6: Variant 17-58998743-T-A is Benign according to our data. Variant chr17-58998743-T-A is described in ClinVar as [Benign]. Clinvar id is 324182.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.377 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TRIM37	NM_015294.6	c.*634A>T		3_prime_UTR_variant	24/24	ENST00000262294.12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TRIM37	ENST00000262294.12	c.*634A>T		3_prime_UTR_variant	24/24	1	NM_015294.6	P1

Frequencies

GnomAD3 genomes AF: 0.343 AC: 52197 AN: 151974 Hom.: 9166 Cov.: 33

Gnomad AFR AF: 0.298

Gnomad AMI AF: 0.225

Gnomad AMR AF: 0.281

Gnomad ASJ AF: 0.429

Gnomad EAS AF: 0.299

Gnomad SAS AF: 0.394

Gnomad FIN AF: 0.358

Gnomad MID AF: 0.446

Gnomad NFE AF: 0.379

Gnomad OTH AF: 0.364

GnomAD4 exome AF: 0.370 AC: 308271 AN: 833130 Hom.: 56973 Cov.: 31 AF XY: 0.370 AC XY: 142450 AN XY: 384746

Gnomad4 AFR exome AF: 0.305

Gnomad4 AMR exome AF: 0.265

Gnomad4 ASJ exome AF: 0.429

Gnomad4 EAS exome AF: 0.307

Gnomad4 SAS exome AF: 0.383

Gnomad4 FIN exome AF: 0.360

Gnomad4 NFE exome AF: 0.371

Gnomad4 OTH exome AF: 0.376

GnomAD4 genome AF: 0.343 AC: 52221 AN: 152092 Hom.: 9175 Cov.: 33 AF XY: 0.342 AC XY: 25408 AN XY: 74340

Gnomad4 AFR AF: 0.298

Gnomad4 AMR AF: 0.281

Gnomad4 ASJ AF: 0.429

Gnomad4 EAS AF: 0.298

Gnomad4 SAS AF: 0.392

Gnomad4 FIN AF: 0.358

Gnomad4 NFE AF: 0.379

Gnomad4 OTH AF: 0.371

Alfa AF: 0.208 Hom.: 459

Bravo AF: 0.333

Asia WGS AF: 0.343 AC: 1190 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Mulibrey nanism syndrome Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 12, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
Cadd	Benign	3.7
Dann	Benign	0.58

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: rs28475409; hg19: chr17-57076104;