rs6681721

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

• chr1-100144083-C-G
• chr1-100144083-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2 PP3

The NM_019083.3(TRMT13):​c.757C>G​(p.Leu253Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic 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 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.01
• 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: Uncertain_significance. The variant received 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.838

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>G	p.Leu253Val	missense	Exon 9 of 11	NP_061956.2	Q9NUP7-1
	TRMT13	NM_001393409.1		c.715C>G	p.Leu239Val	missense	Exon 9 of 11	NP_001380338.1
	TRMT13	NM_001393410.1		c.643C>G	p.Leu215Val	missense	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>G	p.Leu253Val	missense	Exon 9 of 11	ENSP00000359160.2	Q9NUP7-1
	TRMT13	ENST00000962881.1		c.715C>G	p.Leu239Val	missense	Exon 9 of 11	ENSP00000632940.1
	TRMT13	ENST00000482437.5	TSL:2	n.*566C>G		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
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.050	T
BayesDel_noAF	Benign	-0.31
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.035	T
Eigen	Uncertain	0.30
Eigen_PC	Uncertain	0.30
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Benign	0.79	T
M_CAP	Benign	0.025	T
MetaRNN	Pathogenic	0.84	D
MetaSVM	Benign	-0.91	T
MutationAssessor	Benign	1.7	L
PhyloP100		2.0
PrimateAI	Uncertain	0.49	T
PROVEAN	Benign	-1.4	N
REVEL	Benign	0.15
Sift	Benign	0.12	T
Sift4G	Benign	0.19	T
Polyphen		0.99	D
Vest4		0.48
MutPred		0.64		Gain of methylation at K257 (P = 0.0778)
MVP		0.59
MPC		0.66
ClinPred		0.84	D
GERP RS		3.9
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.15
gMVP		0.46
Mutation Taster		=31/69	disease causing

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.090		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;