1-100144085-A-C

Variant names:

• chr1-100144085-A-C
• NM_019083.3:c.759A>C
• TRMT13 p.Leu253Leu

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_019083.3(TRMT13):​c.759A>C​(p.Leu253Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 32)
• Consequence: TRMT13 NM_019083.3 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0670
• Publications: 0 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: Likely_benign. The variant received -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.64).
• BP7: Synonymous conserved (PhyloP=0.067 with no splicing effect.

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.759A>C	p.Leu253Leu	synonymous	Exon 9 of 11	NP_061956.2	Q9NUP7-1
	TRMT13	NM_001393409.1		c.717A>C	p.Leu239Leu	synonymous	Exon 9 of 11	NP_001380338.1
	TRMT13	NM_001393410.1		c.645A>C	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.759A>C	p.Leu253Leu	synonymous	Exon 9 of 11	ENSP00000359160.2	Q9NUP7-1
	TRMT13	ENST00000962881.1		c.717A>C	p.Leu239Leu	synonymous	Exon 9 of 11	ENSP00000632940.1
	TRMT13	ENST00000482437.5	TSL:2	n.*568A>C		non_coding_transcript_exon	Exon 8 of 8	ENSP00000432616.1	Q9NUP7-2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.64
CADD	Benign	6.0
DANN	Benign	0.68
PhyloP100		0.067
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=100/0	polymorphism

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr1-100609641;