NM_152307.3:c.307C>T

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3

The NM_152307.3(TRMT61A):​c.307C>T​(p.Pro103Ser) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000943 in 1,590,560 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 34)
Exomes 𝑓: 0.0000097 ( 0 hom. )

Consequence

TRMT61A
NM_152307.3 missense

Scores

5
9
5

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.61
Variant links:
Genes affected
TRMT61A (HGNC:23790): (tRNA methyltransferase 61A) Enables mRNA (adenine-N1-)-methyltransferase activity. Involved in mRNA methylation. Predicted to be located in nucleoplasm. Predicted to be part of tRNA (m1A) methyltransferase complex. Predicted to be active in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 3 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.767

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
TRMT61ANM_152307.3 linkc.307C>T p.Pro103Ser missense_variant Exon 2 of 4 ENST00000389749.9 NP_689520.2 Q96FX7A0A024R6Q2

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
TRMT61AENST00000389749.9 linkc.307C>T p.Pro103Ser missense_variant Exon 2 of 4 1 NM_152307.3 ENSP00000374399.4 Q96FX7
TRMT61AENST00000299202.4 linkc.34+1024C>T intron_variant Intron 1 of 2 1 ENSP00000299202.4 H0Y2Q1

Frequencies

GnomAD3 genomes
AF:
0.00000657
AC:
1
AN:
152242
Hom.:
0
Cov.:
34
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
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:
0.0000147
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.00000411
AC:
1
AN:
243376
Hom.:
0
AF XY:
0.00
AC XY:
0
AN XY:
132328
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:
0.00000919
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000973
AC:
14
AN:
1438318
Hom.:
0
Cov.:
35
AF XY:
0.00000704
AC XY:
5
AN XY:
710242
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:
0.0000191
Gnomad4 NFE exome
AF:
0.00000914
Gnomad4 OTH exome
AF:
0.0000506
GnomAD4 genome
AF:
0.00000657
AC:
1
AN:
152242
Hom.:
0
Cov.:
34
AF XY:
0.0000134
AC XY:
1
AN XY:
74386
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000147
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.00000378
ESP6500AA
AF:
0.00
AC:
0
ESP6500EA
AF:
0.000118
AC:
1
ExAC
AF:
0.00000825
AC:
1

ClinVar

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

Submissions by phenotype

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

The c.307C>T (p.P103S) alteration is located in exon 2 (coding exon 1) of the TRMT61A gene. This alteration results from a C to T substitution at nucleotide position 307, causing the proline (P) at amino acid position 103 to be replaced by a serine (S). 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
0.39
BayesDel_addAF
Uncertain
0.13
D
BayesDel_noAF
Uncertain
-0.050
CADD
Pathogenic
28
DANN
Pathogenic
1.0
DEOGEN2
Benign
0.33
T
Eigen
Pathogenic
0.75
Eigen_PC
Pathogenic
0.69
FATHMM_MKL
Uncertain
0.91
D
LIST_S2
Uncertain
0.97
D
M_CAP
Benign
0.049
D
MetaRNN
Pathogenic
0.77
D
MetaSVM
Benign
-0.54
T
MutationAssessor
Uncertain
2.8
M
PrimateAI
Uncertain
0.72
T
PROVEAN
Pathogenic
-6.9
D
REVEL
Uncertain
0.43
Sift
Uncertain
0.025
D
Sift4G
Benign
0.068
T
Polyphen
0.99
D
Vest4
0.79
MVP
0.60
MPC
1.4
ClinPred
0.99
D
GERP RS
4.4
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
Varity_R
0.87
gMVP
0.88

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: rs375622926; hg19: chr14-103996622; API