Variant 12-57780484-T-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_015433.3(EEF1AKMT3):c.519T>A(p.His173Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,876 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

EEF1AKMT3
NM_015433.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -1.61

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:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.02915427).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
EEF1AKMT3	NM_015433.3 linkuse as main transcript	c.519T>A	p.His173Gln	missense_variant	3/3	ENST00000300209.13
EEF1AKMT3	NM_206914.2 linkuse as main transcript	c.*208T>A		3_prime_UTR_variant	4/4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
EEF1AKMT3	ENST00000300209.13 linkuse as main transcript	c.519T>A	p.His173Gln	missense_variant	3/3	1	NM_015433.3	P1	Q96AZ1-1
EEF1AKMT3	ENST00000333012.5 linkuse as main transcript	c.*208T>A		3_prime_UTR_variant	4/4	1			Q96AZ1-2
EEF1AKMT3	ENST00000551420.1 linkuse as main transcript	c.-25T>A		5_prime_UTR_variant	3/3	2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461876

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

727238

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:

0.00

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

Cov.:

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

May 30, 2024

The c.519T>A (p.H173Q) alteration is located in exon 3 (coding exon 3) of the METTL21B gene. This alteration results from a T to A substitution at nucleotide position 519, causing the histidine (H) at amino acid position 173 to be replaced by a glutamine (Q). 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

0.089

BayesDel_addAF

Benign

-0.32

BayesDel_noAF

Benign

-0.70

CADD

Benign

4.7

DANN

Benign

0.70

DEOGEN2

Benign

0.00032

Eigen

Benign

-1.1

Eigen_PC

Benign

-0.95

FATHMM_MKL

Benign

0.040

LIST_S2

Benign

0.49

M_CAP

Benign

0.0028

MetaRNN

Benign

0.029

MetaSVM

Benign

-1.0

MutationTaster

Benign

0.58

D;N;N

PrimateAI

Benign

0.40

PROVEAN

Benign

0.94

REVEL

Benign

0.018

Sift

Benign

0.73

Sift4G

Benign

0.70

Polyphen

0.0

Vest4

0.083

MutPred

0.40

Loss of catalytic residue at G174 (P = 0.0699);

MVP

0.055

MPC

0.63

ClinPred

0.020

GERP RS

-1.2

Varity_R

0.19

gMVP

0.34

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

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over