rs2296926

Variant names:

• chr14-60976821-C-T
• rs2296926
• NM_020810.3:c.792+693G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_020810.3(TRMT5):​c.792+693G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.642 in 151,930 control chromosomes in the GnomAD database, including 31,639 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.64 (31639 hom., cov: 31)
• Consequence: TRMT5 NM_020810.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.339
• Publications: 6 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: Labcorp Genetics (formerly Invitae), Ambry Genetics, Orphanet

ENSG00000258892 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.66).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.688 is higher than 0.05.

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TRMT5	NM_020810.3	MANE Select	c.792+693G>A		intron	N/A	NP_065861.3	Q32P41
	TRMT5	NM_001350253.1		c.876+693G>A		intron	N/A	NP_001337182.1
	TRMT5	NM_001350254.1		c.873+693G>A		intron	N/A	NP_001337183.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TRMT5	ENST00000261249.7	TSL:1 MANE Select	c.792+693G>A		intron	N/A	ENSP00000261249.6	Q32P41
	TRMT5	ENST00000928589.1		c.792+693G>A		intron	N/A	ENSP00000598648.1
	ENSG00000258892	ENST00000553946.1	TSL:5	n.123-5687C>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.642 AC: 97464 AN: 151810 Hom.: 31640 Cov.: 31

Gnomad AFR AF: 0.560

Gnomad AMI AF: 0.748

Gnomad AMR AF: 0.645

Gnomad ASJ AF: 0.603

Gnomad EAS AF: 0.599

Gnomad SAS AF: 0.529

Gnomad FIN AF: 0.707

Gnomad MID AF: 0.617

Gnomad NFE AF: 0.693

Gnomad OTH AF: 0.655

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.642 AC: 97505 AN: 151930 Hom.: 31639 Cov.: 31 AF XY: 0.641 AC XY: 47582 AN XY: 74250

African (AFR) AF: 0.559 AC: 23156 AN: 41394

American (AMR) AF: 0.645 AC: 9845 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.603 AC: 2094 AN: 3472

East Asian (EAS) AF: 0.598 AC: 3087 AN: 5164

South Asian (SAS) AF: 0.530 AC: 2548 AN: 4812

European-Finnish (FIN) AF: 0.707 AC: 7465 AN: 10566

Middle Eastern (MID) AF: 0.612 AC: 180 AN: 294

European-Non Finnish (NFE) AF: 0.693 AC: 47075 AN: 67936

Other (OTH) AF: 0.651 AC: 1373 AN: 2110

Alfa AF: 0.673 Hom.: 57456

Bravo AF: 0.636

Asia WGS AF: 0.565 AC: 1963 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.66
CADD	Benign	5.6
DANN	Benign	0.58
PhyloP100		0.34
Mutation Taster		=100/0	polymorphism (auto)

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: rs2296926; hg19: chr14-61443539;