8-124451487-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_017956.4(TRMT12):​c.560C>T​(p.Pro187Leu) variant causes a missense change. The variant allele was found at a frequency of 0.00000137 in 1,461,886 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

TRMT12
NM_017956.4 missense

Scores

4
11
4

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.12
Variant links:
Genes affected
TRMT12 (HGNC:26091): (tRNA methyltransferase 12 homolog) Wybutosine (yW) is a hypermodified guanosine at the 3-prime position adjacent to the anticodon of phenylalanine tRNA that stabilizes codon-anticodon interactions during decoding on the ribosome. TRMT12 is the human homolog of a yeast gene essential for yW synthesis (Noma and Suzuki, 2006).[supplied by OMIM, Mar 2008]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
TRMT12NM_017956.4 linkc.560C>T p.Pro187Leu missense_variant Exon 1 of 1 ENST00000328599.4 NP_060426.2 Q53H54

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
TRMT12ENST00000328599.4 linkc.560C>T p.Pro187Leu missense_variant Exon 1 of 1 6 NM_017956.4 ENSP00000329858.3 Q53H54
TRMT12ENST00000521443.1 linkn.438+230C>T intron_variant Intron 1 of 1 4
TRMT12ENST00000522518.1 linkn.330+230C>T intron_variant Intron 1 of 2 3 ENSP00000429771.1 E5RHH6

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
AF:
0.00000137
AC:
2
AN:
1461886
Hom.:
0
Cov.:
33
AF XY:
0.00000275
AC XY:
2
AN XY:
727246
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:
0.0000116
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
8.99e-7
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 10, 2024
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.560C>T (p.P187L) alteration is located in exon 1 (coding exon 1) of the TRMT12 gene. This alteration results from a C to T substitution at nucleotide position 560, causing the proline (P) at amino acid position 187 to be replaced by a leucine (L). 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
0.38
BayesDel_addAF
Uncertain
0.11
D
BayesDel_noAF
Benign
-0.090
CADD
Pathogenic
26
DANN
Uncertain
1.0
DEOGEN2
Benign
0.085
T
Eigen
Pathogenic
0.81
Eigen_PC
Pathogenic
0.68
FATHMM_MKL
Uncertain
0.79
D
LIST_S2
Uncertain
0.91
D
M_CAP
Uncertain
0.087
D
MetaRNN
Uncertain
0.71
D
MetaSVM
Benign
-0.52
T
MutationAssessor
Pathogenic
4.0
H
PrimateAI
Uncertain
0.56
T
PROVEAN
Pathogenic
-6.6
D
REVEL
Uncertain
0.43
Sift
Uncertain
0.0020
D
Sift4G
Uncertain
0.0030
D
Polyphen
1.0
D
Vest4
0.65
MutPred
0.35
Loss of disorder (P = 0.0302);
MVP
0.30
MPC
0.86
ClinPred
1.0
D
GERP RS
4.8
Varity_R
0.57
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

No publications associated with this variant yet.

Other links and lift over

hg19: chr8-125463728; API