chr1-185120198-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_030934.5(TRMT1L):​c.2023G>A​(p.Val675Ile) variant causes a missense change. The variant allele was found at a frequency of 0.00000558 in 1,612,802 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0000055 ( 0 hom. )

Consequence

TRMT1L
NM_030934.5 missense

Scores

1
18

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.71
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 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.11894339).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
TRMT1LNM_030934.5 linkc.2023G>A p.Val675Ile missense_variant Exon 15 of 15 ENST00000367506.10 NP_112196.3 Q7Z2T5-1
TRMT1LNM_001202423.2 linkc.1555G>A p.Val519Ile missense_variant Exon 15 of 15 NP_001189352.1 Q7Z2T5B4DXX1
TRMT1LXM_047431291.1 linkc.1555G>A p.Val519Ile missense_variant Exon 15 of 15 XP_047287247.1
TRMT1LXM_047431292.1 linkc.1555G>A p.Val519Ile missense_variant Exon 15 of 15 XP_047287248.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
TRMT1LENST00000367506.10 linkc.2023G>A p.Val675Ile missense_variant Exon 15 of 15 1 NM_030934.5 ENSP00000356476.5 Q7Z2T5-1
TRMT1LENST00000465827.1 linkn.561G>A non_coding_transcript_exon_variant Exon 2 of 2 2

Frequencies

GnomAD3 genomes
AF:
0.00000657
AC:
1
AN:
152152
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.0000656
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000199
AC:
5
AN:
251170
Hom.:
0
AF XY:
0.0000147
AC XY:
2
AN XY:
135756
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.000145
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:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000548
AC:
8
AN:
1460650
Hom.:
0
Cov.:
31
AF XY:
0.00000413
AC XY:
3
AN XY:
726684
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.000157
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:
9.00e-7
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.00000657
AC:
1
AN:
152152
Hom.:
0
Cov.:
32
AF XY:
0.00
AC XY:
0
AN XY:
74330
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.0000656
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Nov 10, 2024
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.2023G>A (p.V675I) alteration is located in exon 15 (coding exon 15) of the TRMT1L gene. This alteration results from a G to A substitution at nucleotide position 2023, causing the valine (V) at amino acid position 675 to be replaced by an isoleucine (I). 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
0.054
BayesDel_addAF
Benign
-0.36
T
BayesDel_noAF
Benign
-0.49
CADD
Benign
16
DANN
Benign
0.88
DEOGEN2
Benign
0.15
T
Eigen
Benign
-0.43
Eigen_PC
Benign
-0.19
FATHMM_MKL
Uncertain
0.92
D
LIST_S2
Benign
0.82
T
M_CAP
Benign
0.0026
T
MetaRNN
Benign
0.12
T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
0.74
N
PrimateAI
Benign
0.38
T
PROVEAN
Benign
0.22
N
REVEL
Benign
0.042
Sift
Benign
0.60
T
Sift4G
Benign
0.29
T
Polyphen
0.0020
B
Vest4
0.13
MutPred
0.51
Loss of loop (P = 0.1242);
MVP
0.043
MPC
0.31
ClinPred
0.076
T
GERP RS
4.2
Varity_R
0.023
gMVP
0.24

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

LitVar

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

Other links and lift over

dbSNP: rs1046962945; hg19: chr1-185089330; API