12-57779146-C-T

Variant names:

• chr12-57779146-C-T
• rs10877019
• NM_015433.3:c.290-1109C>T

Variant summary

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

The NM_015433.3(EEF1AKMT3):​c.290-1109C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.267 in 152,072 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: 31)
• Consequence: EEF1AKMT3 NM_015433.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.156
• 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=-0.88).
• 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: 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.290-1109C>T		intron	N/A	NP_056248.2
	EEF1AKMT3	NM_206914.2		c.429-1109C>T		intron	N/A	NP_996797.1	Q96AZ1-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EEF1AKMT3	ENST00000300209.13	TSL:1 MANE Select	c.290-1109C>T		intron	N/A	ENSP00000300209.8	Q96AZ1-1
	EEF1AKMT3	ENST00000333012.5	TSL:1	c.429-1109C>T		intron	N/A	ENSP00000327425.5	Q96AZ1-2
	ENSG00000257921	ENST00000546504.1	TSL:2	c.77-3964C>T		intron	N/A	ENSP00000449544.1	H0YIJ7

Frequencies

GnomAD3 genomes AF: 0.267 AC: 40510 AN: 151954 Hom.: 6789 Cov.: 31

Gnomad AFR AF: 0.0825

Gnomad AMI AF: 0.386

Gnomad AMR AF: 0.256

Gnomad ASJ AF: 0.286

Gnomad EAS AF: 0.652

Gnomad SAS AF: 0.498

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: 0.267 AC: 40529 AN: 152072 Hom.: 6792 Cov.: 31 AF XY: 0.275 AC XY: 20433 AN XY: 74306

African (AFR) AF: 0.0825 AC: 3426 AN: 41512

American (AMR) AF: 0.257 AC: 3925 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.286 AC: 992 AN: 3472

East Asian (EAS) AF: 0.652 AC: 3375 AN: 5178

South Asian (SAS) AF: 0.498 AC: 2399 AN: 4814

European-Finnish (FIN) AF: 0.378 AC: 3977 AN: 10534

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

European-Non Finnish (NFE) AF: 0.317 AC: 21539 AN: 67964

Other (OTH) AF: 0.238 AC: 502 AN: 2108

Alfa AF: 0.203 Hom.: 1828

Bravo AF: 0.248

Asia WGS AF: 0.523 AC: 1816 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	6.1
DANN	Benign	0.67
PhyloP100		0.16
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: rs10877019; hg19: chr12-58172929;