1-185137734-A-C

Position:

• chr1-185137734-A-C

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The ENST00000367506.10(TRMT1L):​c.1385T>G​(p.Val462Gly) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: TRMT1L ENST00000367506.10 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.31

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 Uncertain_significance. Variant got 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.866

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TRMT1L	NM_030934.5	c.1385T>G	p.Val462Gly	missense_variant	10/15	ENST00000367506.10	NP_112196.3
TRMT1L	NM_001202423.2	c.917T>G	p.Val306Gly	missense_variant	10/15		NP_001189352.1
TRMT1L	XM_047431291.1	c.917T>G	p.Val306Gly	missense_variant	10/15		XP_047287247.1
TRMT1L	XM_047431292.1	c.917T>G	p.Val306Gly	missense_variant	10/15		XP_047287248.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TRMT1L	ENST00000367506.10	c.1385T>G	p.Val462Gly	missense_variant	10/15	1	NM_030934.5	ENSP00000356476	P1
TRMT1L	ENST00000458395.1	c.257T>G	p.Val86Gly	missense_variant	2/4	3		ENSP00000414339

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 31, 2023

The c.1385T>G (p.V462G) alteration is located in exon 10 (coding exon 10) of the TRMT1L gene. This alteration results from a T to G substitution at nucleotide position 1385, causing the valine (V) at amino acid position 462 to be replaced by a glycine (G). 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	Pathogenic	0.92
BayesDel_addAF	Pathogenic	0.46	D
BayesDel_noAF	Pathogenic	0.42
CADD	Pathogenic	28
DANN	Uncertain	1.0
DEOGEN2	Pathogenic	0.87	D;.
Eigen	Pathogenic	0.83
Eigen_PC	Pathogenic	0.80
FATHMM_MKL	Pathogenic	1.0	D
LIST_S2	Uncertain	0.89	D;D
M_CAP	Benign	0.062	D
MetaRNN	Pathogenic	0.87	D;D
MetaSVM	Uncertain	-0.017	T
MutationAssessor	Pathogenic	3.2	M;.
MutationTaster	Benign	1.0	D;D
PrimateAI	Uncertain	0.69	T
PROVEAN	Uncertain	-4.2	D;D
REVEL	Pathogenic	0.89
Sift	Uncertain	0.0040	D;D
Sift4G	Uncertain	0.0090	D;D
Polyphen		1.0	D;.
Vest4		0.58
MutPred		0.64		Loss of stability (P = 9e-04);.;
MVP		0.47
MPC		1.0
ClinPred		0.99	D
GERP RS		5.8
Varity_R		0.96
gMVP		0.95

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: chr1-185106866;