8-124451196-C-T

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate

The NM_017956.4(TRMT12):​c.269C>T​(p.Pro90Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000149 in 1,614,136 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.000039 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000012 ( 0 hom. )

Consequence

TRMT12
NM_017956.4 missense

Scores

19

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -3.29
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 Likely_benign. Variant got -4 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.017768323).
BP6
Variant 8-124451196-C-T is Benign according to our data. Variant chr8-124451196-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 2405009.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
TRMT12NM_017956.4 linkc.269C>T p.Pro90Leu 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.269C>T p.Pro90Leu missense_variant Exon 1 of 1 6 NM_017956.4 ENSP00000329858.3 Q53H54
TRMT12ENST00000521443.1 linkn.377C>T non_coding_transcript_exon_variant Exon 1 of 2 4
TRMT12ENST00000522518.1 linkn.269C>T non_coding_transcript_exon_variant Exon 1 of 3 3 ENSP00000429771.1 E5RHH6

Frequencies

GnomAD3 genomes
AF:
0.0000394
AC:
6
AN:
152134
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000196
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:
0.0000441
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000279
AC:
7
AN:
250972
Hom.:
0
AF XY:
0.0000147
AC XY:
2
AN XY:
135626
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.0000289
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:
0.0000530
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000123
AC:
18
AN:
1461884
Hom.:
0
Cov.:
41
AF XY:
0.00000963
AC XY:
7
AN XY:
727244
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.0000894
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000232
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000719
Gnomad4 OTH exome
AF:
0.0000662
GnomAD4 genome
AF:
0.0000394
AC:
6
AN:
152252
Hom.:
0
Cov.:
32
AF XY:
0.0000269
AC XY:
2
AN XY:
74442
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.000196
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000441
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000564
Hom.:
0
Bravo
AF:
0.0000793
ExAC
AF:
0.0000330
AC:
4
EpiCase
AF:
0.000164
EpiControl
AF:
0.0000593

ClinVar

Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Benign:1
Apr 28, 2022
Ambry Genetics
Significance: Likely benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.062
BayesDel_addAF
Benign
-0.46
T
BayesDel_noAF
Benign
-0.76
CADD
Benign
0.037
DANN
Benign
0.87
DEOGEN2
Benign
0.0044
T
Eigen
Benign
-2.0
Eigen_PC
Benign
-2.0
FATHMM_MKL
Benign
0.0036
N
LIST_S2
Benign
0.55
T
M_CAP
Benign
0.0024
T
MetaRNN
Benign
0.018
T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
-0.79
N
PrimateAI
Benign
0.24
T
PROVEAN
Benign
-1.0
N
REVEL
Benign
0.013
Sift
Benign
0.25
T
Sift4G
Benign
0.24
T
Polyphen
0.0010
B
Vest4
0.044
MutPred
0.20
Loss of glycosylation at T87 (P = 0.0474);
MVP
0.043
MPC
0.23
ClinPred
0.082
T
GERP RS
-9.1
Varity_R
0.029
gMVP
0.15

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: rs564386653; hg19: chr8-125463437; API