chr14-60979582-C-CTATT

Variant names:

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

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. 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

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]

ENSG00000258892 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TRMT5	NM_020810.3	c.312_315dupAATA	p.Val106AsnfsTer4	frameshift_variant	Exon 2 of 5	ENST00000261249.7	NP_065861.3
TRMT5	NM_001350253.1	c.396_399dupAATA	p.Val134AsnfsTer4	frameshift_variant	Exon 2 of 5		NP_001337182.1
TRMT5	NM_001350254.1	c.393_396dupAATA	p.Val133AsnfsTer4	frameshift_variant	Exon 2 of 5		NP_001337183.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TRMT5	ENST00000261249.7	c.312_315dupAATA	p.Val106AsnfsTer4	frameshift_variant	Exon 2 of 5	1	NM_020810.3	ENSP00000261249.6
TRMT5	ENST00000553903.1	c.396_399dupAATA	p.Val134AsnfsTer4	frameshift_variant	Exon 2 of 2	4		ENSP00000452567.1
TRMT5	ENST00000555420.1	c.393_396dupAATA	p.Val133AsnfsTer4	frameshift_variant	Exon 2 of 2	4		ENSP00000451666.1
ENSG00000258892	ENST00000553946.1	n.123-2924_123-2921dupATTT		intron_variant	Intron 1 of 1	5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs755184077; hg19: chr14-61446300;