chr1-185140145-C-G

Variant names:

• chr1-185140145-C-G
• rs1032164560
• NM_030934.5:c.937G>C

Variant summary

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

The NM_030934.5(TRMT1L):​c.937G>C​(p.Val313Leu) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: TRMT1L NM_030934.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.69

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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TRMT1L	NM_030934.5	c.937G>C	p.Val313Leu	missense_variant	Exon 8 of 15	ENST00000367506.10	NP_112196.3
TRMT1L	NM_001202423.2	c.469G>C	p.Val157Leu	missense_variant	Exon 8 of 15		NP_001189352.1
TRMT1L	XM_047431291.1	c.469G>C	p.Val157Leu	missense_variant	Exon 8 of 15		XP_047287247.1
TRMT1L	XM_047431292.1	c.469G>C	p.Val157Leu	missense_variant	Exon 8 of 15		XP_047287248.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TRMT1L	ENST00000367506.10	c.937G>C	p.Val313Leu	missense_variant	Exon 8 of 15	1	NM_030934.5	ENSP00000356476.5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

Bravo AF: 0.0000113

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Nov 26, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.937G>C (p.V313L) alteration is located in exon 8 (coding exon 8) of the TRMT1L gene. This alteration results from a G to C substitution at nucleotide position 937, causing the valine (V) at amino acid position 313 to be replaced by a leucine (L). 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	Uncertain	0.40
BayesDel_addAF	Uncertain	0.074	D
BayesDel_noAF	Benign	-0.13
CADD	Uncertain	26
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.43	T
Eigen	Uncertain	0.23
Eigen_PC	Uncertain	0.40
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.91	D
M_CAP	Benign	0.010	T
MetaRNN	Uncertain	0.56	D
MetaSVM	Benign	-0.67	T
MutationAssessor	Uncertain	2.8	M
PrimateAI	Uncertain	0.66	T
PROVEAN	Benign	-1.5	N
REVEL	Benign	0.25
Sift	Uncertain	0.015	D
Sift4G	Uncertain	0.018	D
Polyphen		0.16	B
Vest4		0.55
MutPred		0.79		Gain of disorder (P = 0.3543);
MVP		0.13
MPC		0.73
ClinPred		0.95	D
GERP RS		6.1
Varity_R		0.46
gMVP		0.87

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.22		Details are displayed if max score is > 0.2
DS_AG_spliceai		0.22		Position offset: -15

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs1032164560; hg19: chr1-185109277;