Genetic Variant TRMT1L:p.Thr600Ala (chr1-185123881-T-C) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_030934.5(TRMT1L):c.1798A>G(p.Thr600Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000294 in 1,362,860 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: 0.0000029 ( 0 hom. )

Consequence

TRMT1L
NM_030934.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.0450

Publications

0 publications found

Variant links:

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]

TRMT1L links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.08944011).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TRMT1L	NM_030934.5 link	c.1798A>G	p.Thr600Ala	missense_variant	Exon 13 of 15	ENST00000367506.10	NP_112196.3	Q7Z2T5-1
TRMT1L	NM_001202423.2 link	c.1330A>G	p.Thr444Ala	missense_variant	Exon 13 of 15		NP_001189352.1	Q7Z2T5B4DXX1
TRMT1L	XM_047431291.1 link	c.1330A>G	p.Thr444Ala	missense_variant	Exon 13 of 15		XP_047287247.1
TRMT1L	XM_047431292.1 link	c.1330A>G	p.Thr444Ala	missense_variant	Exon 13 of 15		XP_047287248.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TRMT1L	ENST00000367506.10 link	c.1798A>G	p.Thr600Ala	missense_variant	Exon 13 of 15	1	NM_030934.5	ENSP00000356476.5		Q7Z2T5-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00

AC:

AN:

143146

AF XY:

0.00

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000293

AC:

AN:

1362860

Hom.:

Cov.:

AF XY:

0.00000297

AC XY:

AN XY:

674084

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

29932

American (AMR)

AF:

0.00

AC:

AN:

26756

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

24442

East Asian (EAS)

AF:

0.00

AC:

AN:

35694

South Asian (SAS)

AF:

0.0000546

AC:

AN:

73214

European-Finnish (FIN)

AF:

0.00

AC:

AN:

47728

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5588

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1062972

Other (OTH)

AF:

0.00

AC:

AN:

56534

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.438

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

May 23, 2024

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The c.1798A>G (p.T600A) alteration is located in exon 13 (coding exon 13) of the TRMT1L gene. This alteration results from a A to G substitution at nucleotide position 1798, causing the threonine (T) at amino acid position 600 to be replaced by an alanine (A). 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

0.060

BayesDel_addAF

Benign

-0.28

BayesDel_noAF

Benign

-0.63

CADD

Benign

(source)

DANN

Benign

0.96

DEOGEN2

Benign

0.12

Eigen

Benign

-0.45

Eigen_PC

Benign

-0.33

FATHMM_MKL

Benign

0.68

LIST_S2

Benign

0.47

M_CAP

Benign

0.0037

MetaRNN

Benign

0.089

MetaSVM

Benign

-0.94

MutationAssessor

Benign

0.22

PhyloP100

-0.045

PrimateAI

Benign

0.33

PROVEAN

Benign

-0.57

REVEL

Benign

0.053

Sift

Benign

0.077

Sift4G

Benign

0.53

Polyphen

0.0020

Vest4

0.063

MutPred

0.36

Loss of glycosylation at T600 (P = 0.0923);

MVP

0.043

MPC

0.31

ClinPred

0.086

GERP RS

1.0

Varity_R

0.028

gMVP

0.20

Mutation Taster

=93/7

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over