12-57776552-A-G

Variant names:

• chr12-57776552-A-G
• rs11172333
• NM_015433.3:c.289+3424A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000300209.13(EEF1AKMT3):​c.289+3424A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.266 in 152,104 control chromosomes in the GnomAD database, including 6,792 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 0.27 (6792 hom., cov: 32)
• Consequence: EEF1AKMT3 ENST00000300209.13 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.874
• Publications: 27 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.77).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.633 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000300209.13. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EEF1AKMT3	NM_015433.3	MANE Select	c.289+3424A>G		intron	N/A	NP_056248.2
	EEF1AKMT3	NM_206914.2		c.428+1785A>G		intron	N/A	NP_996797.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EEF1AKMT3	ENST00000300209.13	TSL:1 MANE Select	c.289+3424A>G		intron	N/A	ENSP00000300209.8
	EEF1AKMT3	ENST00000333012.5	TSL:1	c.428+1785A>G		intron	N/A	ENSP00000327425.5
	ENSG00000257921	ENST00000546504.1	TSL:2	c.76+3424A>G		intron	N/A	ENSP00000449544.1

Frequencies

GnomAD3 genomes AF: 0.266 AC: 40401 AN: 151986 Hom.: 6790 Cov.: 32

Gnomad AFR AF: 0.0793

Gnomad AMI AF: 0.385

Gnomad AMR AF: 0.256

Gnomad ASJ AF: 0.286

Gnomad EAS AF: 0.651

Gnomad SAS AF: 0.499

Gnomad FIN AF: 0.378

Gnomad MID AF: 0.139

Gnomad NFE AF: 0.317

Gnomad OTH AF: 0.240

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

GnomAD4 genome AF: 0.266 AC: 40408 AN: 152104 Hom.: 6792 Cov.: 32 AF XY: 0.274 AC XY: 20385 AN XY: 74368

African (AFR) AF: 0.0790 AC: 3281 AN: 41508

American (AMR) AF: 0.257 AC: 3916 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.286 AC: 992 AN: 3466

East Asian (EAS) AF: 0.651 AC: 3373 AN: 5178

South Asian (SAS) AF: 0.499 AC: 2407 AN: 4820

European-Finnish (FIN) AF: 0.378 AC: 4000 AN: 10586

Middle Eastern (MID) AF: 0.146 AC: 43 AN: 294

European-Non Finnish (NFE) AF: 0.317 AC: 21542 AN: 67960

Other (OTH) AF: 0.238 AC: 503 AN: 2114

Alfa AF: 0.230 Hom.: 2299

Bravo AF: 0.247

Asia WGS AF: 0.519 AC: 1802 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	4.9
DANN	Benign	0.90
PhyloP100		-0.87
Mutation Taster		=100/0	polymorphism (auto)

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: rs11172333; hg19: chr12-58170335;