chr1-185120474-C-T

Variant names:

• chr1-185120474-C-T
• rs1652471892
• NM_030934.5:c.1858G>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_030934.5(TRMT1L):​c.1858G>A​(p.Gly620Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000208 in 1,445,326 control chromosomes in the GnomAD database, with no homozygous occurrence. 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)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: TRMT1L NM_030934.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.418
• Publications: 0 publications found

Genes affected

TRMT1L (HGNC:16782): (tRNA methyltransferase 1 like) This gene encodes a protein that has some similarity to N2,N2-dimethylguanosine tRNA methyltransferase from other organisms. Studies of the mouse ortholog have shown that this protein plays a role in motor coordination and exploratory behavior, and it may also be involved in modulating postnatal neuronal functions. Alternatively spliced transcripts have been identified for this gene. [provided by RefSeq, Jan 2011]

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.047449708).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_030934.5. 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
	TRMT1L	NM_030934.5	MANE Select	c.1858G>A	p.Gly620Ser	missense	Exon 14 of 15	NP_112196.3
	TRMT1L	NM_001202423.2		c.1390G>A	p.Gly464Ser	missense	Exon 14 of 15	NP_001189352.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TRMT1L	ENST00000367506.10	TSL:1 MANE Select	c.1858G>A	p.Gly620Ser	missense	Exon 14 of 15	ENSP00000356476.5	Q7Z2T5-1
	TRMT1L	ENST00000942796.1		c.1921G>A	p.Gly641Ser	missense	Exon 15 of 16	ENSP00000612855.1
	TRMT1L	ENST00000860207.1		c.1855G>A	p.Gly619Ser	missense	Exon 14 of 15	ENSP00000530266.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000208 AC: 3 AN: 1445326 Hom.: 0 Cov.: 31 AF XY: 0.00000139 AC XY: 1 AN XY: 718658

African (AFR) AF: 0.00 AC: 0 AN: 32818

American (AMR) AF: 0.00 AC: 0 AN: 41396

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25728

East Asian (EAS) AF: 0.00 AC: 0 AN: 38896

South Asian (SAS) AF: 0.00 AC: 0 AN: 82370

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52892

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5440

European-Non Finnish (NFE) AF: 0.00000181 AC: 2 AN: 1106176

Other (OTH) AF: 0.0000168 AC: 1 AN: 59610

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.074
BayesDel_addAF	Benign	-0.29	T
BayesDel_noAF	Benign	-0.66
CADD	Benign	16
DANN	Benign	0.94
DEOGEN2	Benign	0.093	T
Eigen	Benign	-0.62
Eigen_PC	Benign	-0.37
FATHMM_MKL	Benign	0.29	N
LIST_S2	Benign	0.63	T
M_CAP	Benign	0.0023	T
MetaRNN	Benign	0.047	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-1.1	N
PhyloP100		0.42
PrimateAI	Benign	0.26	T
PROVEAN	Benign	0.55	N
REVEL	Benign	0.18
Sift	Benign	0.40	T
Sift4G	Benign	0.76	T
Polyphen		0.0	B
Vest4		0.15
MutPred		0.34		Gain of methylation at K624 (P = 0.1009)
MVP		0.043
MPC		0.32
ClinPred		0.34	T
GERP RS		5.0
Varity_R		0.047
gMVP		0.24
Mutation Taster		=91/9	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

Other links and lift over

dbSNP: rs1652471892; hg19: chr1-185089606;