rs2296926

Positions:

• chr14-60976821-C-T

Variant summary

Our verdict is Benign. Variant got -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

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]

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TRMT5	NM_020810.3	c.792+693G>A		intron_variant		ENST00000261249.7	NP_065861.3
TRMT5	NM_001350253.1	c.876+693G>A		intron_variant			NP_001337182.1
TRMT5	NM_001350254.1	c.873+693G>A		intron_variant			NP_001337183.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TRMT5	ENST00000261249.7	c.792+693G>A		intron_variant		1	NM_020810.3	ENSP00000261249	P1

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

Gnomad4 AFR AF: 0.559

Gnomad4 AMR AF: 0.645

Gnomad4 ASJ AF: 0.603

Gnomad4 EAS AF: 0.598

Gnomad4 SAS AF: 0.530

Gnomad4 FIN AF: 0.707

Gnomad4 NFE AF: 0.693

Gnomad4 OTH AF: 0.651

Alfa AF: 0.683 Hom.: 41742

Bravo AF: 0.636

Asia WGS AF: 0.565 AC: 1963 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.66
CADD	Benign	5.6
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: rs2296926; hg19: chr14-61443539;