rs914

Variant names:

• chr17-58998352-T-C
• rs914
• NM_015294.6:c.*1025A>G

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_015294.6(TRIM37):​c.*1025A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0048 in 985,450 control chromosomes in the GnomAD database, including 11 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★).

• Frequency:
  • Genomes: 𝑓 0.0028 (2 hom., cov: 33)
  • Exomes 𝑓: 0.0052 (9 hom.)
• Consequence: TRIM37 NM_015294.6 3_prime_UTR
• Clinical Significance: Uncertain significance criteria provided, multiple submitters, no conflicts U:2
• Conservation: PhyloP100: -0.0150
• Publications: 7 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

ENSG00000303842 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -8 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.76).
• BS2: High Homozygotes in GnomAd4 at 2 AR gene

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.*1025A>G		3_prime_UTR	Exon 24 of 24	NP_056109.1	O94972-1
	TRIM37	NM_001353084.2		c.*1025A>G		3_prime_UTR	Exon 24 of 24	NP_001340013.1
	TRIM37	NM_001353086.2		c.*1025A>G		3_prime_UTR	Exon 23 of 23	NP_001340015.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TRIM37	ENST00000262294.12	TSL:1 MANE Select	c.*1025A>G		3_prime_UTR	Exon 24 of 24	ENSP00000262294.7	O94972-1
	TRIM37	ENST00000393066.7	TSL:1	c.2891+1029A>G		intron	N/A	ENSP00000376785.3	O94972-1
	TRIM37	ENST00000577554.5	TSL:1	n.*3675A>G		non_coding_transcript_exon	Exon 24 of 24	ENSP00000462340.1	J3KS72

Frequencies

GnomAD3 genomes AF: 0.00276 AC: 421 AN: 152266 Hom.: 2 Cov.: 33

Gnomad AFR AF: 0.000723

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00190

Gnomad ASJ AF: 0.00144

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00373

Gnomad FIN AF: 0.00132

Gnomad MID AF: 0.0190

Gnomad NFE AF: 0.00456

Gnomad OTH AF: 0.00430

GnomAD4 exome AF: 0.00517 AC: 4303 AN: 833066 Hom.: 9 Cov.: 29 AF XY: 0.00514 AC XY: 1976 AN XY: 384694

African (AFR) AF: 0.000887 AC: 14 AN: 15786

American (AMR) AF: 0.00407 AC: 4 AN: 984

Ashkenazi Jewish (ASJ) AF: 0.00252 AC: 13 AN: 5152

East Asian (EAS) AF: 0.000275 AC: 1 AN: 3630

South Asian (SAS) AF: 0.00492 AC: 81 AN: 16460

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 276

Middle Eastern (MID) AF: 0.00617 AC: 10 AN: 1620

European-Non Finnish (NFE) AF: 0.00535 AC: 4076 AN: 761862

Other (OTH) AF: 0.00381 AC: 104 AN: 27296

GnomAD4 genome AF: 0.00278 AC: 423 AN: 152384 Hom.: 2 Cov.: 33 AF XY: 0.00243 AC XY: 181 AN XY: 74522

African (AFR) AF: 0.000721 AC: 30 AN: 41590

American (AMR) AF: 0.00189 AC: 29 AN: 15310

Ashkenazi Jewish (ASJ) AF: 0.00144 AC: 5 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5194

South Asian (SAS) AF: 0.00373 AC: 18 AN: 4826

European-Finnish (FIN) AF: 0.00132 AC: 14 AN: 10630

Middle Eastern (MID) AF: 0.0204 AC: 6 AN: 294

European-Non Finnish (NFE) AF: 0.00459 AC: 312 AN: 68044

Other (OTH) AF: 0.00426 AC: 9 AN: 2114

Alfa AF: 0.00375 Hom.: 0

Bravo AF: 0.00261

Asia WGS AF: 0.00289 AC: 10 AN: 3478

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	1	-	Mulibrey nanism syndrome (1)
-	1	-	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.76
CADD	Benign	4.1
DANN	Benign	0.79
PhyloP100		-0.015
Mutation Taster		=100/0	polymorphism

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

Other links and lift over

dbSNP: rs914; hg19: chr17-57075713;