2-207613438-G-A
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Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4
The NM_001127395.5(METTL21A):c.265C>T(p.His89Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000568 in 1,584,616 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.000026 ( 0 hom., cov: 33)
Exomes 𝑓: 0.0000035 ( 0 hom. )
Consequence
METTL21A
NM_001127395.5 missense
NM_001127395.5 missense
Scores
7
12
Clinical Significance
Conservation
PhyloP100: 3.09
Genes affected
METTL21A (HGNC:30476): (methyltransferase 21A, HSPA lysine) Enables ATPase binding activity; Hsp70 protein binding activity; and protein-lysine N-methyltransferase activity. Involved in peptidyl-lysine methylation. Part of protein-containing complex. [provided by Alliance of Genome Resources, Apr 2022]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 1 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.28200698).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
METTL21A | NM_001127395.5 | c.265C>T | p.His89Tyr | missense_variant | 4/4 | ENST00000411432.6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
METTL21A | ENST00000411432.6 | c.265C>T | p.His89Tyr | missense_variant | 4/4 | 2 | NM_001127395.5 | P1 |
Frequencies
GnomAD3 genomes AF: 0.0000263 AC: 4AN: 152192Hom.: 0 Cov.: 33
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GnomAD3 exomes AF: 0.00000453 AC: 1AN: 220572Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 118528
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GnomAD4 exome AF: 0.00000349 AC: 5AN: 1432424Hom.: 0 Cov.: 33 AF XY: 0.00000281 AC XY: 2AN XY: 710594
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GnomAD4 genome AF: 0.0000263 AC: 4AN: 152192Hom.: 0 Cov.: 33 AF XY: 0.0000269 AC XY: 2AN XY: 74342
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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 | Mar 20, 2023 | The c.265C>T (p.H89Y) alteration is located in exon 4 (coding exon 3) of the METTL21A gene. This alteration results from a C to T substitution at nucleotide position 265, causing the histidine (H) at amino acid position 89 to be replaced by a tyrosine (Y). 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
Benign
DANN
Uncertain
DEOGEN2
Benign
T;T;T;T;T;T
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
LIST_S2
Benign
T;.;D;.;.;.
M_CAP
Benign
T
MetaRNN
Benign
T;T;T;T;T;T
MetaSVM
Benign
T
MutationAssessor
Uncertain
M;M;.;M;M;M
MutationTaster
Benign
D;D;D;D;N;N;N;N;N;N
PrimateAI
Uncertain
T
PROVEAN
Uncertain
D;D;N;D;D;D
REVEL
Benign
Sift
Benign
D;D;D;D;D;D
Sift4G
Benign
T;T;T;T;T;T
Polyphen
B;B;.;B;B;B
Vest4
MutPred
Loss of sheet (P = 0.1398);Loss of sheet (P = 0.1398);.;Loss of sheet (P = 0.1398);Loss of sheet (P = 0.1398);Loss of sheet (P = 0.1398);
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