rs145666727
Positions:
Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PP3_ModerateBS2
The NM_015935.5(METTL13):c.1631G>A(p.Arg544Gln) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000285 in 1,614,212 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 risk factor (no stars).
Frequency
Genomes: 𝑓 0.000053 ( 0 hom., cov: 33)
Exomes 𝑓: 0.000026 ( 0 hom. )
Consequence
METTL13
NM_015935.5 missense
NM_015935.5 missense
Scores
8
8
3
Clinical Significance
Conservation
PhyloP100: 9.55
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 -2 ACMG points.
PP3
MetaRNN computational evidence supports a deleterious effect, 0.855
BS2
High AC in GnomAd4 at 8 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
METTL13 | NM_015935.5 | c.1631G>A | p.Arg544Gln | missense_variant | 6/8 | ENST00000361735.4 | NP_057019.3 | |
METTL13 | NM_014955.3 | c.1373G>A | p.Arg458Gln | missense_variant | 6/8 | NP_055770.1 | ||
METTL13 | NM_001007239.2 | c.1163G>A | p.Arg388Gln | missense_variant | 6/8 | NP_001007240.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
METTL13 | ENST00000361735.4 | c.1631G>A | p.Arg544Gln | missense_variant | 6/8 | 1 | NM_015935.5 | ENSP00000354920.3 | ||
METTL13 | ENST00000367737.9 | c.1163G>A | p.Arg388Gln | missense_variant | 6/8 | 1 | ENSP00000356711.5 | |||
METTL13 | ENST00000362019.7 | c.1373G>A | p.Arg458Gln | missense_variant | 6/8 | 2 | ENSP00000355393.3 | |||
METTL13 | ENST00000466643.1 | n.225G>A | non_coding_transcript_exon_variant | 2/4 | 2 |
Frequencies
GnomAD3 genomes AF: 0.0000525 AC: 8AN: 152246Hom.: 0 Cov.: 33
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GnomAD3 exomes AF: 0.0000318 AC: 8AN: 251438Hom.: 0 AF XY: 0.0000221 AC XY: 3AN XY: 135898
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GnomAD4 exome AF: 0.0000260 AC: 38AN: 1461848Hom.: 0 Cov.: 31 AF XY: 0.0000289 AC XY: 21AN XY: 727222
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GnomAD4 genome AF: 0.0000525 AC: 8AN: 152364Hom.: 0 Cov.: 33 AF XY: 0.0000403 AC XY: 3AN XY: 74506
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ClinVar
Significance: risk factor
Submissions summary: Other:1
Revision: no assertion criteria provided
LINK: link
Submissions by phenotype
Deafness, autosomal recessive 26, modifier of Other:1
risk factor, no assertion criteria provided | literature only | OMIM | Oct 02, 2024 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
CADD
Pathogenic
DANN
Pathogenic
DEOGEN2
Benign
.;.;T
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Pathogenic
D
LIST_S2
Uncertain
D;D;D
M_CAP
Uncertain
D
MetaRNN
Pathogenic
D;D;D
MetaSVM
Uncertain
D
MutationAssessor
Uncertain
.;.;M
PrimateAI
Uncertain
T
PROVEAN
Uncertain
D;D;D
REVEL
Pathogenic
Sift
Uncertain
D;T;D
Sift4G
Uncertain
D;D;D
Polyphen
1.0
.;D;D
Vest4
MVP
MPC
0.84
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