chr2-28861156-C-T

Position:

• chr2-28861156-C-T

Variant summary

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

The NM_017910.4(TRMT61B):​c.955G>A​(p.Gly319Arg) 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 benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: TRMT61B NM_017910.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.308

Genes affected

TRMT61B (HGNC:26070): (tRNA methyltransferase 61B) Enables mRNA (adenine-N1-)-methyltransferase activity; rRNA (adenine) methyltransferase activity; and tRNA (adenine-N1-)-methyltransferase activity. Involved in mRNA methylation; mitochondrial tRNA methylation; and protein homooligomerization. Located in mitochondrion. [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=0.11898616).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TRMT61B	NM_017910.4	c.955G>A	p.Gly319Arg	missense_variant	3/7	ENST00000306108.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TRMT61B	ENST00000306108.10	c.955G>A	p.Gly319Arg	missense_variant	3/7	1	NM_017910.4	P1
TRMT61B	ENST00000484060.1	n.191G>A		non_coding_transcript_exon_variant	2/4	5
TRMT61B	ENST00000490390.5	n.335G>A		non_coding_transcript_exon_variant	1/3	3
TRMT61B	ENST00000439947.1	c.955G>A	p.Gly319Arg	missense_variant, NMD_transcript_variant	3/6	5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.084
BayesDel_addAF	Benign	-0.22	T
BayesDel_noAF	Benign	-0.56
CADD	Benign	8.6
DANN	Benign	0.82
DEOGEN2	Benign	0.0047	T
Eigen	Benign	-1.0
Eigen_PC	Benign	-0.96
FATHMM_MKL	Benign	0.20	N
LIST_S2	Benign	0.71	T
M_CAP	Benign	0.035	D
MetaRNN	Benign	0.12	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.89	L
MutationTaster	Benign	1.0	N
PrimateAI	Benign	0.36	T
PROVEAN	Benign	-0.63	N
REVEL	Benign	0.12
Sift	Benign	0.12	T
Sift4G	Benign	0.56	T
Polyphen		0.0020	B
Vest4		0.18
MutPred		0.62		Loss of catalytic residue at A320 (P = 0.0981);
MVP		0.35
MPC		0.099
ClinPred		0.048	T
GERP RS		-1.6
Varity_R		0.052
gMVP		0.37

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: chr2-29084022; COSMIC: COSV60258188;