chr1-171784416-C-T
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Variant summary
Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2
The NM_015935.5(METTL13):c.830C>T(p.Thr277Met) variant causes a missense change. The variant allele was found at a frequency of 0.0000305 in 1,542,146 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.000033 ( 0 hom., cov: 33)
Exomes 𝑓: 0.000030 ( 0 hom. )
Consequence
METTL13
NM_015935.5 missense
NM_015935.5 missense
Scores
5
12
Clinical Significance
Conservation
PhyloP100: 3.67
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 Likely_benign. Variant got -6 ACMG points.
BP4
Computational evidence support a benign effect (MetaRNN=0.07484624).
BS2
High AC in GnomAd4 at 5 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
METTL13 | NM_015935.5 | c.830C>T | p.Thr277Met | missense_variant | 2/8 | ENST00000361735.4 | |
METTL13 | NM_014955.3 | c.572C>T | p.Thr191Met | missense_variant | 2/8 | ||
METTL13 | NM_001007239.2 | c.453+377C>T | intron_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
METTL13 | ENST00000361735.4 | c.830C>T | p.Thr277Met | missense_variant | 2/8 | 1 | NM_015935.5 | P1 | |
METTL13 | ENST00000367737.9 | c.453+377C>T | intron_variant | 1 | |||||
METTL13 | ENST00000362019.7 | c.572C>T | p.Thr191Met | missense_variant | 2/8 | 2 | |||
METTL13 | ENST00000485629.1 | n.565+377C>T | intron_variant, non_coding_transcript_variant | 5 |
Frequencies
GnomAD3 genomes AF: 0.0000328 AC: 5AN: 152224Hom.: 0 Cov.: 33
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GnomAD3 exomes AF: 0.000103 AC: 19AN: 184976Hom.: 0 AF XY: 0.0000917 AC XY: 9AN XY: 98178
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GnomAD4 exome AF: 0.0000302 AC: 42AN: 1389922Hom.: 0 Cov.: 34 AF XY: 0.0000380 AC XY: 26AN XY: 683898
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GnomAD4 genome AF: 0.0000328 AC: 5AN: 152224Hom.: 0 Cov.: 33 AF XY: 0.0000403 AC XY: 3AN XY: 74374
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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 | Jul 09, 2021 | The c.830C>T (p.T277M) alteration is located in exon 2 (coding exon 2) of the METTL13 gene. This alteration results from a C to T substitution at nucleotide position 830, causing the threonine (T) at amino acid position 277 to be replaced by a methionine (M). 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
Benign
T
BayesDel_noAF
Benign
CADD
Uncertain
DANN
Uncertain
Eigen
Benign
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
LIST_S2
Uncertain
D;D
M_CAP
Benign
T
MetaRNN
Benign
T;T
MetaSVM
Benign
T
MutationTaster
Benign
D;D;D;D
PrimateAI
Benign
T
PROVEAN
Uncertain
D;D
REVEL
Benign
Sift
Benign
T;D
Sift4G
Benign
T;T
Polyphen
0.65
.;P
Vest4
MutPred
0.31
.;Loss of loop (P = 0.0512);
MVP
MPC
0.26
ClinPred
T
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
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