1-185137684-C-T

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

7
12

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]

Genome browser will be placed here

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
TRMT1LNM_030934.5 linkc.1435G>A p.Ala479Thr missense_variant Exon 10 of 15 ENST00000367506.10 NP_112196.3 Q7Z2T5-1
TRMT1LNM_001202423.2 linkc.967G>A p.Ala323Thr missense_variant Exon 10 of 15 NP_001189352.1 Q7Z2T5B4DXX1
TRMT1LXM_047431291.1 linkc.967G>A p.Ala323Thr missense_variant Exon 10 of 15 XP_047287247.1
TRMT1LXM_047431292.1 linkc.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
TRMT1LENST00000367506.10 linkc.1435G>A p.Ala479Thr missense_variant Exon 10 of 15 1 NM_030934.5 ENSP00000356476.5 Q7Z2T5-1
TRMT1LENST00000458395.1 linkc.307G>A p.Ala103Thr missense_variant Exon 2 of 4 3 ENSP00000414339.1 X6RK96

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD3 exomes
AF:
0.00000398
AC:
1
AN:
251062
Hom.:
0
AF XY:
0.00000737
AC XY:
1
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:
2
AN:
1461830
Hom.:
0
Cov.:
31
AF XY:
0.00000275
AC XY:
2
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.:
32

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
T
BayesDel_noAF
Benign
-0.23
CADD
Benign
21
DANN
Uncertain
1.0
DEOGEN2
Benign
0.33
T;.
Eigen
Uncertain
0.29
Eigen_PC
Uncertain
0.36
FATHMM_MKL
Uncertain
0.97
D
LIST_S2
Benign
0.80
T;T
M_CAP
Benign
0.0085
T
MetaRNN
Benign
0.33
T;T
MetaSVM
Benign
-0.86
T
MutationAssessor
Uncertain
2.3
M;.
PrimateAI
Uncertain
0.59
T
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
D
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.

Other links and lift over

dbSNP: rs1557988401; hg19: chr1-185106816; API