Genetic Variant TRMT1L:p.Ala479Thr (chr1-185137684-C-T) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_030934.5(TRMT1L):c.1435G>A(p.Ala479Thr) variant causes a missense change. The variant allele was found at a frequency of 0.00000137 in 1,461,830 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

TRMT1L
NM_030934.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.93

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:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.32678866).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TRMT1L	NM_030934.5 link	c.1435G>A	p.Ala479Thr	missense_variant	Exon 10 of 15	ENST00000367506.10	NP_112196.3	Q7Z2T5-1
TRMT1L	NM_001202423.2 link	c.967G>A	p.Ala323Thr	missense_variant	Exon 10 of 15		NP_001189352.1	Q7Z2T5B4DXX1
TRMT1L	XM_047431291.1 link	c.967G>A	p.Ala323Thr	missense_variant	Exon 10 of 15		XP_047287247.1
TRMT1L	XM_047431292.1 link	c.967G>A	p.Ala323Thr	missense_variant	Exon 10 of 15		XP_047287248.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TRMT1L	ENST00000367506.10 link	c.1435G>A	p.Ala479Thr	missense_variant	Exon 10 of 15	1	NM_030934.5	ENSP00000356476.5		Q7Z2T5-1
TRMT1L	ENST00000458395.1 link	c.307G>A	p.Ala103Thr	missense_variant	Exon 2 of 4	3		ENSP00000414339.1		X6RK96

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000398

AC:

AN:

251062

Hom.:

AF XY:

0.00000737

AC XY:

AN XY:

135668

show subpopulations

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 SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000882

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000137

AC:

AN:

1461830

Hom.:

Cov.:

AF XY:

0.00000275

AC XY:

AN XY:

727216

show subpopulations

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:

0.00000180

Gnomad4 OTH exome

AF:

0.00

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

Nov 12, 2021

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.1435G>A (p.A479T) alteration is located in exon 10 (coding exon 10) of the TRMT1L gene. This alteration results from a G to A substitution at nucleotide position 1435, causing the alanine (A) at amino acid position 479 to be replaced by a threonine (T). 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

0.10

BayesDel_addAF

Benign

0.0023

BayesDel_noAF

Benign

-0.23

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.33

T;.

Eigen

Uncertain

0.29

Eigen_PC

Uncertain

0.36

FATHMM_MKL

Uncertain

0.97

LIST_S2

Benign

0.80

T;T

M_CAP

Benign

0.0085

MetaRNN

Benign

0.33

T;T

MetaSVM

Benign

-0.86

MutationAssessor

Uncertain

2.3

M;.

PrimateAI

Uncertain

0.59

PROVEAN

Benign

-1.1

N;N

REVEL

Benign

0.088

Sift

Benign

0.21

T;T

Sift4G

Uncertain

0.052

T;T

Polyphen

0.70

P;.

Vest4

0.25

MutPred

0.51

Gain of ubiquitination at K480 (P = 0.0754);.;

MVP

0.13

MPC

0.47

ClinPred

0.80

GERP RS

4.9

Varity_R

0.10

gMVP

0.72

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over