chr1-171784023-T-C
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_015935.5(METTL13):c.437T>C(p.Val146Ala) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,892 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: not found (cov: 33)
Exomes 𝑓: 0.0000014 ( 0 hom. )
Consequence
METTL13
NM_015935.5 missense
NM_015935.5 missense
Scores
1
10
6
Clinical Significance
Conservation
PhyloP100: 7.51
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 2 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
METTL13 | NM_015935.5 | c.437T>C | p.Val146Ala | missense_variant | 2/8 | ENST00000361735.4 | |
METTL13 | NM_014955.3 | c.179T>C | p.Val60Ala | missense_variant | 2/8 | ||
METTL13 | NM_001007239.2 | c.437T>C | p.Val146Ala | missense_variant | 2/8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
METTL13 | ENST00000361735.4 | c.437T>C | p.Val146Ala | missense_variant | 2/8 | 1 | NM_015935.5 | P1 | |
METTL13 | ENST00000367737.9 | c.437T>C | p.Val146Ala | missense_variant | 2/8 | 1 | |||
METTL13 | ENST00000362019.7 | c.179T>C | p.Val60Ala | missense_variant | 2/8 | 2 | |||
METTL13 | ENST00000485629.1 | n.549T>C | non_coding_transcript_exon_variant | 3/4 | 5 |
Frequencies
GnomAD3 genomes ? Cov.: 33
GnomAD3 genomes
?
Cov.:
33
GnomAD4 exome AF: 0.00000137 AC: 2AN: 1461892Hom.: 0 Cov.: 34 AF XY: 0.00 AC XY: 0AN XY: 727248
GnomAD4 exome
AF:
AC:
2
AN:
1461892
Hom.:
Cov.:
34
AF XY:
AC XY:
0
AN XY:
727248
Gnomad4 AFR exome
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Gnomad4 AMR exome
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Gnomad4 EAS exome
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Gnomad4 SAS exome
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Gnomad4 FIN exome
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GnomAD4 genome ? Cov.: 33
GnomAD4 genome
?
Cov.:
33
Bravo
AF:
ESP6500AA
AF:
AC:
0
ESP6500EA
AF:
AC:
1
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 | Mar 01, 2024 | The c.437T>C (p.V146A) alteration is located in exon 2 (coding exon 2) of the METTL13 gene. This alteration results from a T to C substitution at nucleotide position 437, causing the valine (V) at amino acid position 146 to be replaced by an alanine (A). 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
T
BayesDel_noAF
Benign
Cadd
Pathogenic
Dann
Uncertain
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Pathogenic
D
LIST_S2
Uncertain
D;D;D
M_CAP
Benign
D
MetaRNN
Uncertain
T;T;T
MetaSVM
Benign
T
MutationTaster
Benign
D;D;D;N
PrimateAI
Uncertain
T
PROVEAN
Uncertain
D;D;D
REVEL
Benign
Sift
Uncertain
D;T;D
Sift4G
Uncertain
D;D;D
Polyphen
0.0010, 0.70
.;B;P
Vest4
MVP
MPC
0.44
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