1-100144083-C-T

Variant names:

• chr1-100144083-C-T
• rs6681721
• NM_019083.3:c.757C>T

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_Moderate BP7 BA1

The NM_019083.3(TRMT13):​c.757C>T​(p.Leu253Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0449 in 1,611,528 control chromosomes in the GnomAD database, including 1,830 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 0.049 (209 hom., cov: 32)
  • Exomes 𝑓: 0.045 (1621 hom.)
• Consequence: TRMT13 NM_019083.3 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.01
• Publications: 12 publications found

Genes affected

TRMT13 (HGNC:25502): (tRNA methyltransferase 13 homolog) Predicted to enable tRNA methyltransferase activity. Predicted to be involved in tRNA methylation. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Benign. The variant received -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.39).
• BP7: Synonymous conserved (PhyloP=2.01 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0652 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_019083.3. 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
	TRMT13	NM_019083.3	MANE Select	c.757C>T	p.Leu253Leu	synonymous	Exon 9 of 11	NP_061956.2	Q9NUP7-1
	TRMT13	NM_001393409.1		c.715C>T	p.Leu239Leu	synonymous	Exon 9 of 11	NP_001380338.1
	TRMT13	NM_001393410.1		c.643C>T	p.Leu215Leu	synonymous	Exon 7 of 9	NP_001380339.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TRMT13	ENST00000370141.8	TSL:1 MANE Select	c.757C>T	p.Leu253Leu	synonymous	Exon 9 of 11	ENSP00000359160.2	Q9NUP7-1
	TRMT13	ENST00000962881.1		c.715C>T	p.Leu239Leu	synonymous	Exon 9 of 11	ENSP00000632940.1
	TRMT13	ENST00000482437.5	TSL:2	n.*566C>T		non_coding_transcript_exon	Exon 8 of 8	ENSP00000432616.1	Q9NUP7-2

Frequencies

GnomAD3 genomes AF: 0.0487 AC: 7402 AN: 152024 Hom.: 210 Cov.: 32

Gnomad AFR AF: 0.0673

Gnomad AMI AF: 0.0482

Gnomad AMR AF: 0.0330

Gnomad ASJ AF: 0.0133

Gnomad EAS AF: 0.0156

Gnomad SAS AF: 0.0545

Gnomad FIN AF: 0.0407

Gnomad MID AF: 0.0285

Gnomad NFE AF: 0.0462

Gnomad OTH AF: 0.0475

GnomAD2 exomes AF: 0.0379 AC: 9510 AN: 250970 AF XY: 0.0389

Gnomad AFR exome AF: 0.0674

Gnomad AMR exome AF: 0.0174

Gnomad ASJ exome AF: 0.0153

Gnomad EAS exome AF: 0.00468

Gnomad FIN exome AF: 0.0392

Gnomad NFE exome AF: 0.0427

Gnomad OTH exome AF: 0.0371

GnomAD4 exome AF: 0.0445 AC: 64995 AN: 1459386 Hom.: 1621 Cov.: 30 AF XY: 0.0448 AC XY: 32513 AN XY: 726180

African (AFR) AF: 0.0704 AC: 2350 AN: 33402

American (AMR) AF: 0.0194 AC: 868 AN: 44694

Ashkenazi Jewish (ASJ) AF: 0.0154 AC: 403 AN: 26114

East Asian (EAS) AF: 0.0319 AC: 1266 AN: 39638

South Asian (SAS) AF: 0.0548 AC: 4723 AN: 86204

European-Finnish (FIN) AF: 0.0390 AC: 2081 AN: 53370

Middle Eastern (MID) AF: 0.0560 AC: 323 AN: 5764

European-Non Finnish (NFE) AF: 0.0455 AC: 50494 AN: 1109912

Other (OTH) AF: 0.0413 AC: 2487 AN: 60288

GnomAD4 genome AF: 0.0487 AC: 7404 AN: 152142 Hom.: 209 Cov.: 32 AF XY: 0.0487 AC XY: 3624 AN XY: 74368

African (AFR) AF: 0.0673 AC: 2793 AN: 41514

American (AMR) AF: 0.0330 AC: 504 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.0133 AC: 46 AN: 3470

East Asian (EAS) AF: 0.0157 AC: 81 AN: 5172

South Asian (SAS) AF: 0.0541 AC: 261 AN: 4824

European-Finnish (FIN) AF: 0.0407 AC: 431 AN: 10578

Middle Eastern (MID) AF: 0.0238 AC: 7 AN: 294

European-Non Finnish (NFE) AF: 0.0462 AC: 3140 AN: 67992

Other (OTH) AF: 0.0460 AC: 97 AN: 2108

Alfa AF: 0.0437 Hom.: 324

Bravo AF: 0.0465

Asia WGS AF: 0.0320 AC: 111 AN: 3476

EpiCase AF: 0.0412

EpiControl AF: 0.0387

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.39
CADD	Benign	10
DANN	Benign	0.66
PhyloP100		2.0
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs6681721; hg19: chr1-100609639; COSMIC: COSV61583620; COSMIC: COSV61583620;