rs923829

chr12-57780523-T-Achr12-57780523-T-C

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_015433.3(EEF1AKMT3):c.558T>A(p.His186Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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)
• Consequence: EEF1AKMT3 NM_015433.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.46

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]

ACMG classification

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=0.36630616).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
EEF1AKMT3	NM_015433.3	c.558T>A	p.His186Gln	missense_variant	3/3	ENST00000300209.13
EEF1AKMT3	NM_206914.2	c.*247T>A		3_prime_UTR_variant	4/4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
EEF1AKMT3	ENST00000300209.13	c.558T>A	p.His186Gln	missense_variant	3/3	1	NM_015433.3	P1
EEF1AKMT3	ENST00000333012.5	c.*247T>A		3_prime_UTR_variant	4/4	1
EEF1AKMT3	ENST00000551420.1	c.15T>A	p.His5Gln	missense_variant	3/3	2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 62

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.80
BayesDel_addAF	Benign	-0.23	T
BayesDel_noAF	Benign	-0.56
Cadd	Benign	12
Dann	Benign	0.93
Eigen	Benign	-0.67
Eigen_PC	Benign	-0.75
FATHMM_MKL	Benign	0.043	N
LIST_S2	Benign	0.71	T;T
M_CAP	Benign	0.014	T
MetaRNN	Benign	0.37	T;T
MetaSVM	Benign	-1.1	T
MutationTaster	Benign	0.98	P;P;P
PrimateAI	Uncertain	0.58	T
PROVEAN	Pathogenic	-8.0	D;N
REVEL	Benign	0.19
Sift	Pathogenic	0.0	D;T
Sift4G	Pathogenic	0.0	D;T
Polyphen		1.0	.;D
Vest4		0.61
MutPred		0.40		.;Gain of methylation at K181 (P = 0.0859);
MVP		0.092
MPC		1.6
ClinPred		0.97	D
GERP RS		-2.5
Varity_R		0.41
gMVP		0.44

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

Other links and lift over

dbSNP: rs923829; hg19: chr12-58174306;