chr1-185120474-C-T

Variant names:

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

Variant summary

Our verdict is Likely benign. Variant got -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. 15/20 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

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

Verdict is Likely_benign. Variant got -2 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TRMT1L	NM_030934.5	c.1858G>A	p.Gly620Ser	missense_variant	Exon 14 of 15	ENST00000367506.10	NP_112196.3
TRMT1L	NM_001202423.2	c.1390G>A	p.Gly464Ser	missense_variant	Exon 14 of 15		NP_001189352.1
TRMT1L	XM_047431291.1	c.1390G>A	p.Gly464Ser	missense_variant	Exon 14 of 15		XP_047287247.1
TRMT1L	XM_047431292.1	c.1390G>A	p.Gly464Ser	missense_variant	Exon 14 of 15		XP_047287248.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TRMT1L	ENST00000367506.10	c.1858G>A	p.Gly620Ser	missense_variant	Exon 14 of 15	1	NM_030934.5	ENSP00000356476.5
TRMT1L	ENST00000465827.1	n.396G>A		non_coding_transcript_exon_variant	Exon 1 of 2	2

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

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: 0.00000181

Gnomad4 OTH exome AF: 0.0000168

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Jan 18, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.1858G>A (p.G620S) alteration is located in exon 14 (coding exon 14) of the TRMT1L gene. This alteration results from a G to A substitution at nucleotide position 1858, causing the glycine (G) at amino acid position 620 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

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
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

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

LitVar

Other links and lift over

dbSNP: rs1652471892; hg19: chr1-185089606;