3-101565595-A-G
Position:
Variant summary
Our verdict is Uncertain significance. Variant got 5 ACMG points: 5P and 0B. PM2PM5PP5
The NM_017819.4(TRMT10C):āc.814A>Gā(p.Thr272Ala) variant causes a missense change. The variant allele was found at a frequency of 0.00000137 in 1,461,814 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Pathogenic (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. T272S) has been classified as Pathogenic.
Frequency
Genomes: not found (cov: 32)
Exomes š: 0.0000014 ( 0 hom. )
Consequence
TRMT10C
NM_017819.4 missense
NM_017819.4 missense
Scores
3
8
7
Clinical Significance
Conservation
PhyloP100: 7.10
Genes affected
TRMT10C (HGNC:26022): (tRNA methyltransferase 10C, mitochondrial RNase P subunit) This gene encodes the precursor of a subunit of the mitochondrial ribonuclease P, which is involved in 5' processing of mitochondrial tRNAs. The encoded protein may confer RNA-binding capacity to mitochondrial ribonuclease P and may be essential for transcript processing, RNA modification, translation and mitochondrial respiration. [provided by RefSeq, Nov 2012]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 5 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
PM5
Other missense variant is known to change same aminoacid residue: Variant chr3-101565595-A-T is described in Lovd as [Pathogenic].
PP5
Variant 3-101565595-A-G is Pathogenic according to our data. Variant chr3-101565595-A-G is described in ClinVar as [Pathogenic]. Clinvar id is 224317.Status of the report is no_assertion_criteria_provided, 0 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
TRMT10C | NM_017819.4 | c.814A>G | p.Thr272Ala | missense_variant | 2/2 | ENST00000309922.7 | NP_060289.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
TRMT10C | ENST00000309922.7 | c.814A>G | p.Thr272Ala | missense_variant | 2/2 | 1 | NM_017819.4 | ENSP00000312356.6 | ||
TRMT10C | ENST00000495642.1 | c.814A>G | p.Thr272Ala | missense_variant | 2/2 | 3 | ENSP00000419389.1 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD3 genomes
Cov.:
32
GnomAD4 exome AF: 0.00000137 AC: 2AN: 1461814Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0AN XY: 727204
GnomAD4 exome
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2
AN:
1461814
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33
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0
AN XY:
727204
Gnomad4 AFR exome
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GnomAD4 genome Cov.: 32
GnomAD4 genome
Cov.:
32
ClinVar
Significance: Pathogenic
Submissions summary: Pathogenic:2
Revision: no assertion criteria provided
LINK: link
Submissions by phenotype
Mitochondrial disease Pathogenic:1
Pathogenic, no assertion criteria provided | clinical testing | Wellcome Centre for Mitochondrial Research, Newcastle University | Mar 08, 2016 | - - |
Combined oxidative phosphorylation defect type 30 Pathogenic:1
Pathogenic, no assertion criteria provided | literature only | OMIM | Sep 10, 2019 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Uncertain
CADD
Uncertain
DANN
Uncertain
DEOGEN2
Benign
T;.
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Uncertain
D
LIST_S2
Benign
T;T
M_CAP
Benign
T
MetaRNN
Uncertain
D;D
MetaSVM
Benign
T
MutationTaster
Benign
D
PrimateAI
Benign
T
PROVEAN
Uncertain
D;D
REVEL
Uncertain
Sift
Uncertain
D;D
Sift4G
Uncertain
D;D
Polyphen
D;.
Vest4
MutPred
Loss of methylation at K268 (P = 0.085);Loss of methylation at K268 (P = 0.085);
MVP
MPC
ClinPred
D
GERP RS
Varity_R
gMVP
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at