Variant 12-57780519-A-G details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_015433.3(EEF1AKMT3):c.554A>G(p.Glu185Gly) variant causes a missense change. The variant allele was found at a frequency of 0.0000253 in 1,461,838 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.000025 ( 0 hom. )

Consequence

EEF1AKMT3
NM_015433.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.59

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]

EEF1AKMT3 links:

ENSG00000257921 (HGNC:):

ENSG00000257921 links:

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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=0.39571804).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
EEF1AKMT3	NM_015433.3 link	c.554A>G	p.Glu185Gly	missense_variant	3/3	ENST00000300209.13	NP_056248.2
EEF1AKMT3	NM_206914.2 link	c.*243A>G		3_prime_UTR_variant	4/4		NP_996797.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
EEF1AKMT3	ENST00000300209.13 link	c.554A>G	p.Glu185Gly	missense_variant	3/3	1	NM_015433.3	ENSP00000300209.8		Q96AZ1-1
ENSG00000257921	ENST00000546504.1 link	c.77-2591A>G		intron_variant		2		ENSP00000449544.1		H0YIJ7

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000796

AC:

AN:

251246

Hom.:

AF XY:

0.00000736

AC XY:

AN XY:

135816

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000176

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000253

AC:

AN:

1461838

Hom.:

Cov.:

AF XY:

0.0000275

AC XY:

AN XY:

727212

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000333

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000378

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.0000165

AC:

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

Nov 11, 2024

The c.554A>G (p.E185G) alteration is located in exon 3 (coding exon 3) of the METTL21B gene. This alteration results from a A to G substitution at nucleotide position 554, causing the glutamic acid (E) at amino acid position 185 to be replaced by a glycine (G). 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

Pathogenic

0.58

BayesDel_addAF

Benign

-0.087

BayesDel_noAF

Benign

-0.35

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.023

.;T

Eigen

Uncertain

0.57

Eigen_PC

Uncertain

0.59

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Benign

0.75

T;T

M_CAP

Benign

0.034

MetaRNN

Benign

0.40

T;T

MetaSVM

Benign

-1.2

PrimateAI

Uncertain

0.49

PROVEAN

Pathogenic

-7.0

D;D

REVEL

Uncertain

0.31

Sift

Pathogenic

0.0

D;D

Sift4G

Pathogenic

0.0

D;D

Polyphen

0.95

.;P

Vest4

0.56

MVP

0.39

MPC

1.8

ClinPred

0.96

GERP RS

5.2

Varity_R

0.57

gMVP

0.63

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over