chr12-57773057-A-T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_015433.3(EEF1AKMT3):​c.218A>T​(p.Asp73Val) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Consequence

EEF1AKMT3
NM_015433.3 missense

Scores

1
8
9

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.16
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]

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
EEF1AKMT3NM_015433.3 linkuse as main transcriptc.218A>T p.Asp73Val missense_variant 2/3 ENST00000300209.13
EEF1AKMT3NM_206914.2 linkuse as main transcriptc.218A>T p.Asp73Val missense_variant 2/4

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
EEF1AKMT3ENST00000300209.13 linkuse as main transcriptc.218A>T p.Asp73Val missense_variant 2/31 NM_015433.3 P1Q96AZ1-1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Cov.:
32
GnomAD4 genome
Cov.:
32

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 GeneticsAug 08, 2023The c.218A>T (p.D73V) alteration is located in exon 2 (coding exon 2) of the METTL21B gene. This alteration results from a A to T substitution at nucleotide position 218, causing the aspartic acid (D) at amino acid position 73 to be replaced by a valine (V). 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
0.25
BayesDel_addAF
Uncertain
0.016
T
BayesDel_noAF
Benign
-0.22
CADD
Pathogenic
31
DANN
Uncertain
0.99
DEOGEN2
Benign
0.022
.;T;.;.
Eigen
Uncertain
0.42
Eigen_PC
Uncertain
0.41
FATHMM_MKL
Benign
0.70
D
LIST_S2
Benign
0.84
T;T;T;T
M_CAP
Benign
0.071
D
MetaRNN
Uncertain
0.45
T;T;T;T
MetaSVM
Benign
-0.90
T
MutationTaster
Benign
1.0
D;D;D;D
PrimateAI
Uncertain
0.58
T
PROVEAN
Pathogenic
-6.0
D;D;D;D
REVEL
Benign
0.23
Sift
Uncertain
0.0040
D;D;D;.
Sift4G
Uncertain
0.0030
D;T;D;D
Polyphen
0.96, 1.0
.;D;D;.
Vest4
0.43
MutPred
0.54
.;Gain of loop (P = 0.2045);Gain of loop (P = 0.2045);.;
MVP
0.60
MPC
1.9
ClinPred
0.99
D
GERP RS
4.1
Varity_R
0.60
gMVP
0.58

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.010
Details are displayed if max score is > 0.2

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr12-58166840; API