rs377517086

Variant names:

• chr14-103534757-C-G
• NM_152307.3:c.806C>G

Your query was ambiguous. Multiple possible variants found:

• chr14-103534757-C-G
• chr14-103534757-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_152307.3(TRMT61A):​c.806C>G​(p.Thr269Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000696 in 1,436,012 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. T269M) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 34)
  • Exomes 𝑓: 7.0e-7 (0 hom.)
• Consequence: TRMT61A NM_152307.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.95

Genes affected

TRMT61A (HGNC:23790): (tRNA methyltransferase 61A) Enables mRNA (adenine-N1-)-methyltransferase activity. Involved in mRNA methylation. Predicted to be located in nucleoplasm. Predicted to be part of tRNA (m1A) methyltransferase complex. Predicted to be active in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.0942938).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TRMT61A	NM_152307.3	c.806C>G	p.Thr269Arg	missense_variant	Exon 4 of 4	ENST00000389749.9	NP_689520.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TRMT61A	ENST00000389749.9	c.806C>G	p.Thr269Arg	missense_variant	Exon 4 of 4	1	NM_152307.3	ENSP00000374399.4
TRMT61A	ENST00000299202.4	c.509C>G	p.Thr170Arg	missense_variant	Exon 3 of 3	1		ENSP00000299202.4

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome AF: 6.96e-7 AC: 1 AN: 1436012 Hom.: 0 Cov.: 31 AF XY: 0.00000140 AC XY: 1 AN XY: 712938

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 9.07e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 34

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.19
BayesDel_addAF	Benign	-0.22	T
BayesDel_noAF	Benign	-0.55
CADD	Benign	15
DANN	Benign	0.88
DEOGEN2	Benign	0.055	T
Eigen	Benign	-0.69
Eigen_PC	Benign	-0.57
FATHMM_MKL	Uncertain	0.88	D
LIST_S2	Benign	0.69	T
M_CAP	Benign	0.027	D
MetaRNN	Benign	0.094	T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	0.085	N
PrimateAI	Uncertain	0.55	T
PROVEAN	Benign	-0.84	N
REVEL	Benign	0.049
Sift	Benign	0.63	T
Sift4G	Benign	0.56	T
Polyphen		0.43	B
Vest4		0.14
MutPred		0.38		Gain of catalytic residue at R266 (P = 0.0021);
MVP		0.20
MPC		0.58
ClinPred		0.25	T
GERP RS		2.3
Varity_R		0.21
gMVP		0.72

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr14-104001094;