chr12-57772830-T-C

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_015433.3(EEF1AKMT3):ā€‹c.106T>Cā€‹(p.Cys36Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,846 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 (ā˜…).

Frequency

Genomes: not found (cov: 32)
Exomes š‘“: 0.0000014 ( 0 hom. )

Consequence

EEF1AKMT3
NM_015433.3 missense

Scores

10
8

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.82
Variant links:
Genes affected
EEF1AKMT3 (HGNC:24936): (EEF1A lysine methyltransferase 3) Enables heat shock protein binding activity and protein-lysine N-methyltransferase activity. Involved in peptidyl-lysine methylation. Located in several cellular components, including centrosome; chromosome; and nucleoplasm. 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=0.29096085).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
EEF1AKMT3NM_015433.3 linkuse as main transcriptc.106T>C p.Cys36Arg missense_variant 1/3 ENST00000300209.13
EEF1AKMT3NM_206914.2 linkuse as main transcriptc.106T>C p.Cys36Arg missense_variant 1/4

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
EEF1AKMT3ENST00000300209.13 linkuse as main transcriptc.106T>C p.Cys36Arg missense_variant 1/31 NM_015433.3 P1Q96AZ1-1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD3 exomes
AF:
0.00000398
AC:
1
AN:
251232
Hom.:
0
AF XY:
0.00
AC XY:
0
AN XY:
135846
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.0000544
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:
0.00000137
AC:
2
AN:
1461846
Hom.:
0
Cov.:
32
AF XY:
0.00
AC XY:
0
AN XY:
727234
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0000504
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32
Bravo
AF:
0.00000756

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 GeneticsFeb 06, 2024The c.106T>C (p.C36R) alteration is located in exon 1 (coding exon 1) of the METTL21B gene. This alteration results from a T to C substitution at nucleotide position 106, causing the cysteine (C) at amino acid position 36 to be replaced by an arginine (R). 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
Uncertain
0.46
BayesDel_addAF
Uncertain
0.12
D
BayesDel_noAF
Uncertain
-0.070
CADD
Pathogenic
27
DANN
Uncertain
0.99
DEOGEN2
Benign
0.085
T;.
Eigen
Uncertain
0.30
Eigen_PC
Uncertain
0.32
FATHMM_MKL
Benign
0.45
N
LIST_S2
Benign
0.61
T;T
M_CAP
Benign
0.059
D
MetaRNN
Benign
0.29
T;T
MetaSVM
Benign
-1.0
T
MutationTaster
Benign
1.0
D;D;D;D
PrimateAI
Uncertain
0.61
T
PROVEAN
Uncertain
-3.7
D;D
REVEL
Benign
0.24
Sift
Uncertain
0.012
D;D
Sift4G
Uncertain
0.023
D;D
Polyphen
0.92
P;D
Vest4
0.18
MutPred
0.57
Gain of disorder (P = 0.0516);Gain of disorder (P = 0.0516);
MVP
0.38
MPC
2.2
ClinPred
0.98
D
GERP RS
5.3
Varity_R
0.93
gMVP
0.73

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.0
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: rs1334424639; hg19: chr12-58166613; API