2-207613438-G-A

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

Scores

7
12

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.09
Variant links:
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]

Genome browser will be placed here

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
METTL21ANM_001127395.5 linkuse as main transcriptc.265C>T p.His89Tyr missense_variant 4/4 ENST00000411432.6

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
METTL21AENST00000411432.6 linkuse as main transcriptc.265C>T p.His89Tyr missense_variant 4/42 NM_001127395.5 P1Q8WXB1-1

Frequencies

GnomAD3 genomes
AF:
0.0000263
AC:
4
AN:
152192
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.0000965
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.00000453
AC:
1
AN:
220572
Hom.:
0
AF XY:
0.00
AC XY:
0
AN XY:
118528
show subpopulations
Gnomad AFR exome
AF:
0.0000628
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000349
AC:
5
AN:
1432424
Hom.:
0
Cov.:
33
AF XY:
0.00000281
AC XY:
2
AN XY:
710594
show subpopulations
Gnomad4 AFR exome
AF:
0.0000919
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000182
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.0000263
AC:
4
AN:
152192
Hom.:
0
Cov.:
33
AF XY:
0.0000269
AC XY:
2
AN XY:
74342
show subpopulations
Gnomad4 AFR
AF:
0.0000965
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000712
Hom.:
0
Bravo
AF:
0.0000189

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 submitterclinical testingAmbry GeneticsMar 20, 2023The 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: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.14
BayesDel_addAF
Benign
-0.15
T
BayesDel_noAF
Benign
-0.45
CADD
Benign
22
DANN
Uncertain
0.99
DEOGEN2
Benign
0.045
T;T;T;T;T;T
Eigen
Uncertain
0.23
Eigen_PC
Uncertain
0.36
FATHMM_MKL
Uncertain
0.93
D
LIST_S2
Benign
0.35
T;.;D;.;.;.
M_CAP
Benign
0.0047
T
MetaRNN
Benign
0.28
T;T;T;T;T;T
MetaSVM
Benign
-1.1
T
MutationAssessor
Uncertain
2.3
M;M;.;M;M;M
MutationTaster
Benign
1.0
D;D;D;D;N;N;N;N;N;N
PrimateAI
Uncertain
0.55
T
PROVEAN
Uncertain
-2.5
D;D;N;D;D;D
REVEL
Benign
0.083
Sift
Benign
0.050
D;D;D;D;D;D
Sift4G
Benign
0.065
T;T;T;T;T;T
Polyphen
0.30
B;B;.;B;B;B
Vest4
0.27
MutPred
0.38
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
0.32
MPC
0.51
ClinPred
0.63
D
GERP RS
5.5
Varity_R
0.41
gMVP
0.50

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.080
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs955143550; hg19: chr2-208478162; API