NM_020810.3:c.312_315dupAATA

Variant names:

• chr14-60979582-C-CTATT
• rs755184077
• NM_020810.3:c.312_315dupAATA

Variant summary

Our verdict is Pathogenic. The variant received 10 ACMG points: 10P and 0B. PVS1 PM2

The NM_020810.3(TRMT5):​c.312_315dupAATA​(p.Val106AsnfsTer4) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Variant results in nonsense mediated mRNA decay.

• Frequency: Genomes: not found (cov: 32)
• Consequence: TRMT5 NM_020810.3 frameshift
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0630
• Publications: 7 publications found

Genes affected

TRMT5 (HGNC:23141): (tRNA methyltransferase 5) tRNAs contain as many as 13 or 14 nucleotides that are modified posttranscriptionally by enzymes that are highly specific for particular nucleotides in the tRNA structure. TRMT5 methylates the N1 position of guanosine-37 (G37) in selected tRNAs using S-adenosyl methionine (Brule et al., 2004 [PubMed 15248782]).[supplied by OMIM, Mar 2008]

TRMT5 Gene-Disease associations (from GenCC):

• mitochondrial disease

  Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
• combined oxidative phosphorylation defect type 26

  Inheritance: AR Classification: STRONG, MODERATE, SUPPORTIVE Submitted by: Orphanet, Ambry Genetics, Labcorp Genetics (formerly Invitae)

ENSG00000258892 (HGNC:):

ACMG classification

Our verdict: Pathogenic. The variant received 10 ACMG points.

• PVS1: Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_020810.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TRMT5	NM_020810.3	MANE Select	c.312_315dupAATA	p.Val106AsnfsTer4	frameshift	Exon 2 of 5	NP_065861.3
	TRMT5	NM_001350253.1		c.396_399dupAATA	p.Val134AsnfsTer4	frameshift	Exon 2 of 5	NP_001337182.1
	TRMT5	NM_001350254.1		c.393_396dupAATA	p.Val133AsnfsTer4	frameshift	Exon 2 of 5	NP_001337183.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TRMT5	ENST00000261249.7	TSL:1 MANE Select	c.312_315dupAATA	p.Val106AsnfsTer4	frameshift	Exon 2 of 5	ENSP00000261249.6
	TRMT5	ENST00000553903.1	TSL:4	c.396_399dupAATA	p.Val134AsnfsTer4	frameshift	Exon 2 of 2	ENSP00000452567.1
	TRMT5	ENST00000555420.1	TSL:4	c.393_396dupAATA	p.Val133AsnfsTer4	frameshift	Exon 2 of 2	ENSP00000451666.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.063

Splicing

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

Other links and lift over

dbSNP: rs755184077; hg19: chr14-61446300;