rs1958281

Positions:

• chr14-60971588-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_020810.3(TRMT5):​c.*3521C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.924 in 177,264 control chromosomes in the GnomAD database, including 76,318 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 0.92 (64859 hom., cov: 33)
  • Exomes 𝑓: 0.95 (11459 hom.)
• Consequence: TRMT5 NM_020810.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.475

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 Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.06).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.98 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TRMT5	NM_020810.3	c.*3521C>T		3_prime_UTR_variant	5/5	ENST00000261249.7	NP_065861.3
TRMT5	NM_001350253.1	c.*3521C>T		3_prime_UTR_variant	5/5		NP_001337182.1
TRMT5	NM_001350254.1	c.*3521C>T		3_prime_UTR_variant	5/5		NP_001337183.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TRMT5	ENST00000261249	c.*3521C>T		3_prime_UTR_variant	5/5	1	NM_020810.3	ENSP00000261249.6
ENSG00000258892	ENST00000553946.1	n.123-10920G>A		intron_variant		5

Frequencies

GnomAD3 genomes AF: 0.919 AC: 139896 AN: 152180 Hom.: 64815 Cov.: 33

Gnomad AFR AF: 0.835

Gnomad AMI AF: 1.00

Gnomad AMR AF: 0.880

Gnomad ASJ AF: 0.948

Gnomad EAS AF: 0.788

Gnomad SAS AF: 0.763

Gnomad FIN AF: 0.990

Gnomad MID AF: 0.934

Gnomad NFE AF: 0.986

Gnomad OTH AF: 0.923

GnomAD4 exome AF: 0.955 AC: 23836 AN: 24966 Hom.: 11459 Cov.: 0 AF XY: 0.952 AC XY: 16284 AN XY: 17106

Gnomad4 AFR exome AF: 0.796

Gnomad4 AMR exome AF: 0.842

Gnomad4 ASJ exome AF: 0.952

Gnomad4 EAS exome AF: 0.707

Gnomad4 SAS exome AF: 0.783

Gnomad4 FIN exome AF: 0.991

Gnomad4 NFE exome AF: 0.986

Gnomad4 OTH exome AF: 0.944

GnomAD4 genome AF: 0.919 AC: 139999 AN: 152298 Hom.: 64859 Cov.: 33 AF XY: 0.915 AC XY: 68158 AN XY: 74466

Gnomad4 AFR AF: 0.835

Gnomad4 AMR AF: 0.880

Gnomad4 ASJ AF: 0.948

Gnomad4 EAS AF: 0.788

Gnomad4 SAS AF: 0.765

Gnomad4 FIN AF: 0.990

Gnomad4 NFE AF: 0.986

Gnomad4 OTH AF: 0.919

Alfa AF: 0.953 Hom.: 21514

Bravo AF: 0.910

Asia WGS AF: 0.771 AC: 2683 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.1
CADD	Benign	0.10
DANN	Benign	0.47

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: rs1958281; hg19: chr14-61438306;