chr1-171783873-C-A
Position:
Variant summary
Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3
The NM_015935.5(METTL13):c.287C>A(p.Pro96His) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: not found (cov: 32)
Consequence
METTL13
NM_015935.5 missense
NM_015935.5 missense
Scores
5
7
5
Clinical Significance
Conservation
PhyloP100: 5.71
Genes affected
METTL13 (HGNC:24248): (methyltransferase 13, eEF1A N-terminus and K55) Predicted to enable methyltransferase activity. Involved in negative regulation of cell cycle G1/S phase transition and negative regulation of transcription by RNA polymerase II. Predicted to be located in mitochondrion and nucleus. [provided by Alliance of Genome Resources, Apr 2022]
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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/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
METTL13 | NM_015935.5 | c.287C>A | p.Pro96His | missense_variant | 2/8 | ENST00000361735.4 | |
METTL13 | NM_014955.3 | c.29C>A | p.Pro10His | missense_variant | 2/8 | ||
METTL13 | NM_001007239.2 | c.287C>A | p.Pro96His | missense_variant | 2/8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
METTL13 | ENST00000361735.4 | c.287C>A | p.Pro96His | missense_variant | 2/8 | 1 | NM_015935.5 | P1 | |
METTL13 | ENST00000367737.9 | c.287C>A | p.Pro96His | missense_variant | 2/8 | 1 | |||
METTL13 | ENST00000362019.7 | c.29C>A | p.Pro10His | missense_variant | 2/8 | 2 | |||
METTL13 | ENST00000485629.1 | n.399C>A | non_coding_transcript_exon_variant | 3/4 | 5 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD3 genomes
Cov.:
32
GnomAD4 exome Cov.: 31
GnomAD4 exome
Cov.:
31
GnomAD4 genome Cov.: 32
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
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Feb 28, 2023 | The c.287C>A (p.P96H) alteration is located in exon 2 (coding exon 2) of the METTL13 gene. This alteration results from a C to A substitution at nucleotide position 287, causing the proline (P) at amino acid position 96 to be replaced by a histidine (H). 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
Uncertain
D
BayesDel_noAF
Uncertain
CADD
Pathogenic
DANN
Uncertain
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Pathogenic
D
LIST_S2
Benign
T;T;T
M_CAP
Benign
D
MetaRNN
Pathogenic
D;D;D
MetaSVM
Benign
T
MutationTaster
Benign
D;D;D;D
PrimateAI
Uncertain
T
PROVEAN
Pathogenic
D;D;D
REVEL
Uncertain
Sift
Uncertain
D;D;D
Sift4G
Uncertain
D;D;D
Polyphen
0.98, 1.0
.;D;D
Vest4
MutPred
0.44
.;Gain of MoRF binding (P = 0.0652);Gain of MoRF binding (P = 0.0652);
MVP
MPC
0.87
ClinPred
D
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
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
Publications
No publications associated with this variant yet.