12-57780523-T-G

Variant names:

• chr12-57780523-T-G
• rs923829
• NM_015433.3:c.558T>G

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_015433.3(EEF1AKMT3):​c.558T>G​(p.His186Gln) 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 1,461,622 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict 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: 6.8e-7 (0 hom.)
• Consequence: EEF1AKMT3 NM_015433.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.46
• Publications: 0 publications found

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]

ENSG00000257921 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.37136698).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015433.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EEF1AKMT3	NM_015433.3	MANE Select	c.558T>G	p.His186Gln	missense	Exon 3 of 3	NP_056248.2
	EEF1AKMT3	NM_206914.2		c.*247T>G		3_prime_UTR	Exon 4 of 4	NP_996797.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EEF1AKMT3	ENST00000300209.13	TSL:1 MANE Select	c.558T>G	p.His186Gln	missense	Exon 3 of 3	ENSP00000300209.8
	EEF1AKMT3	ENST00000333012.5	TSL:1	c.*247T>G		3_prime_UTR	Exon 4 of 4	ENSP00000327425.5
	ENSG00000257921	ENST00000546504.1	TSL:2	c.77-2587T>G		intron	N/A	ENSP00000449544.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461622 Hom.: 0 Cov.: 62 AF XY: 0.00000138 AC XY: 1 AN XY: 727092

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44656

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26132

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86254

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53372

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 8.99e-7 AC: 1 AN: 1111872

Other (OTH) AF: 0.00 AC: 0 AN: 60388

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

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	0.92
DEOGEN2	Benign	0.0049	T
Eigen	Benign	-0.67
Eigen_PC	Benign	-0.75
FATHMM_MKL	Benign	0.053	N
LIST_S2	Benign	0.71	T
M_CAP	Benign	0.014	T
MetaRNN	Benign	0.37	T
MetaSVM	Benign	-1.1	T
PhyloP100		-1.5
PrimateAI	Uncertain	0.58	T
PROVEAN	Pathogenic	-8.0	D
REVEL	Benign	0.19
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0	D
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		0.98	D
GERP RS		-2.5
Varity_R		0.41
gMVP		0.44
Mutation Taster		=69/31	polymorphism

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

Other links and lift over

dbSNP: rs923829; hg19: chr12-58174306;