rs1958281

Variant names:

• chr14-60971588-G-A
• rs1958281
• NM_020810.3:c.*3521C>T

Variant summary

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

The ENST00000261249.7(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 ENST00000261249.7 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.475
• Publications: 4 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: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000261249.7. 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.*3521C>T		3_prime_UTR	Exon 5 of 5	NP_065861.3
	TRMT5	NM_001350253.1		c.*3521C>T		3_prime_UTR	Exon 5 of 5	NP_001337182.1
	TRMT5	NM_001350254.1		c.*3521C>T		3_prime_UTR	Exon 5 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.*3521C>T		3_prime_UTR	Exon 5 of 5	ENSP00000261249.6
	ENSG00000258892	ENST00000553946.1	TSL:5	n.123-10920G>A		intron	N/A

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

African (AFR) AF: 0.796 AC: 242 AN: 304

American (AMR) AF: 0.842 AC: 527 AN: 626

Ashkenazi Jewish (ASJ) AF: 0.952 AC: 474 AN: 498

East Asian (EAS) AF: 0.707 AC: 472 AN: 668

South Asian (SAS) AF: 0.783 AC: 1458 AN: 1862

European-Finnish (FIN) AF: 0.991 AC: 947 AN: 956

Middle Eastern (MID) AF: 0.942 AC: 98 AN: 104

European-Non Finnish (NFE) AF: 0.986 AC: 18517 AN: 18782

Other (OTH) AF: 0.944 AC: 1101 AN: 1166

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

African (AFR) AF: 0.835 AC: 34701 AN: 41534

American (AMR) AF: 0.880 AC: 13468 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.948 AC: 3291 AN: 3472

East Asian (EAS) AF: 0.788 AC: 4079 AN: 5176

South Asian (SAS) AF: 0.765 AC: 3695 AN: 4828

European-Finnish (FIN) AF: 0.990 AC: 10512 AN: 10622

Middle Eastern (MID) AF: 0.939 AC: 276 AN: 294

European-Non Finnish (NFE) AF: 0.986 AC: 67123 AN: 68042

Other (OTH) AF: 0.919 AC: 1942 AN: 2114

Alfa AF: 0.952 Hom.: 27058

Bravo AF: 0.910

Asia WGS AF: 0.771 AC: 2683 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.1
CADD	Benign	0.10
DANN	Benign	0.47
PhyloP100		0.47
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: rs1958281; hg19: chr14-61438306;