12-57774005-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_015433.3(EEF1AKMT3):c.289+877A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.283 in 152,150 control chromosomes in the GnomAD database, including 7,071 homozygotes. 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: 𝑓 0.28 (7071 hom., cov: 32)
• Consequence: EEF1AKMT3 NM_015433.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.294

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 Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.57).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.634 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
EEF1AKMT3	NM_015433.3	c.289+877A>G		intron_variant		ENST00000300209.13
EEF1AKMT3	NM_206914.2	c.290-624A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
EEF1AKMT3	ENST00000300209.13	c.289+877A>G		intron_variant		1	NM_015433.3	P1

Frequencies

GnomAD3 genomes AF: 0.283 AC: 42996 AN: 152032 Hom.: 7067 Cov.: 32

Gnomad AFR AF: 0.139

Gnomad AMI AF: 0.384

Gnomad AMR AF: 0.262

Gnomad ASJ AF: 0.286

Gnomad EAS AF: 0.652

Gnomad SAS AF: 0.498

Gnomad FIN AF: 0.377

Gnomad MID AF: 0.139

Gnomad NFE AF: 0.317

Gnomad OTH AF: 0.255

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.283 AC: 43014 AN: 152150 Hom.: 7071 Cov.: 32 AF XY: 0.291 AC XY: 21622 AN XY: 74378

Gnomad4 AFR AF: 0.139

Gnomad4 AMR AF: 0.263

Gnomad4 ASJ AF: 0.286

Gnomad4 EAS AF: 0.652

Gnomad4 SAS AF: 0.498

Gnomad4 FIN AF: 0.377

Gnomad4 NFE AF: 0.317

Gnomad4 OTH AF: 0.253

Alfa AF: 0.299 Hom.: 6536

Bravo AF: 0.267

Asia WGS AF: 0.525 AC: 1822 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.57
Cadd	Benign	12
Dann	Benign	0.92

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: rs10877015; hg19: chr12-58167788;