chr10-17149114-G-C
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Variant summary
Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate
The NM_004412.7(TRDMT1):āc.1102C>Gā(p.Gln368Glu) variant causes a missense change. The variant allele was found at a frequency of 0.0000248 in 1,610,882 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 (ā ).
Frequency
Genomes: š 0.000013 ( 0 hom., cov: 33)
Exomes š: 0.000026 ( 0 hom. )
Consequence
TRDMT1
NM_004412.7 missense
NM_004412.7 missense
Scores
9
7
3
Clinical Significance
Conservation
PhyloP100: 6.84
Genes affected
TRDMT1 (HGNC:2977): (tRNA aspartic acid methyltransferase 1) This gene encodes a protein responsible for the methylation of aspartic acid transfer RNA, specifically at the cytosine-38 residue in the anticodon loop. This enzyme also possesses residual DNA-(cytosine-C5) methyltransferase activity. While similar in sequence and structure to DNA cytosine methyltransferases, this gene is distinct and highly conserved in its function among taxa. [provided by RefSeq, Jun 2010]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 4 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.915
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TRDMT1 | NM_004412.7 | c.1102C>G | p.Gln368Glu | missense_variant | 11/11 | ENST00000377799.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TRDMT1 | ENST00000377799.8 | c.1102C>G | p.Gln368Glu | missense_variant | 11/11 | 1 | NM_004412.7 | P1 | |
TRDMT1 | ENST00000354631.7 | c.*1122C>G | 3_prime_UTR_variant, NMD_transcript_variant | 12/12 | 1 | ||||
TRDMT1 | ENST00000495022.5 | c.*767C>G | 3_prime_UTR_variant, NMD_transcript_variant | 9/9 | 2 |
Frequencies
GnomAD3 genomes AF: 0.0000131 AC: 2AN: 152124Hom.: 0 Cov.: 33
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GnomAD3 exomes AF: 0.00000401 AC: 1AN: 249680Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 135070
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GnomAD4 exome AF: 0.0000260 AC: 38AN: 1458758Hom.: 0 Cov.: 29 AF XY: 0.0000179 AC XY: 13AN XY: 725778
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GnomAD4 genome AF: 0.0000131 AC: 2AN: 152124Hom.: 0 Cov.: 33 AF XY: 0.0000135 AC XY: 1AN XY: 74306
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Nov 07, 2023 | The c.1102C>G (p.Q368E) alteration is located in exon 11 (coding exon 11) of the TRDMT1 gene. This alteration results from a C to G substitution at nucleotide position 1102, causing the glutamine (Q) at amino acid position 368 to be replaced by a glutamic acid (E). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
CADD
Pathogenic
DANN
Uncertain
DEOGEN2
Pathogenic
D
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Pathogenic
D
LIST_S2
Uncertain
D
M_CAP
Uncertain
D
MetaRNN
Pathogenic
D
MetaSVM
Uncertain
D
MutationAssessor
Pathogenic
M
MutationTaster
Benign
D;D;D;D;D;D
PrimateAI
Uncertain
T
PROVEAN
Benign
N
REVEL
Pathogenic
Sift
Uncertain
D
Sift4G
Uncertain
D
Polyphen
D
Vest4
MutPred
Loss of MoRF binding (P = 0.0512);
MVP
MPC
ClinPred
D
GERP RS
Varity_R
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at