12-57772620-T-G

Position:

• chr12-57772620-T-G

Variant summary

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

The NM_015433.3(EEF1AKMT3):​c.-105T>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.338 in 1,273,888 control chromosomes in the GnomAD database, including 79,311 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 0.29 (7491 hom., cov: 33)
  • Exomes 𝑓: 0.34 (71820 hom.)
• Consequence: EEF1AKMT3 NM_015433.3 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.635

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=-0.83).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.636 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
EEF1AKMT3	NM_015433.3	c.-105T>G		5_prime_UTR_variant	1/3	ENST00000300209.13
EEF1AKMT3	NM_206914.2	c.-105T>G		5_prime_UTR_variant	1/4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
EEF1AKMT3	ENST00000300209.13	c.-105T>G		5_prime_UTR_variant	1/3	1	NM_015433.3	P1
EEF1AKMT3	ENST00000548256.5	c.52-397T>G		intron_variant		4
EEF1AKMT3	ENST00000551420.1	c.-367+223T>G		intron_variant		2
EEF1AKMT3	ENST00000552307.1			upstream_gene_variant		5

Frequencies

GnomAD3 genomes AF: 0.293 AC: 44579 AN: 151964 Hom.: 7472 Cov.: 33

Gnomad AFR AF: 0.164

Gnomad AMI AF: 0.384

Gnomad AMR AF: 0.268

Gnomad ASJ AF: 0.286

Gnomad EAS AF: 0.655

Gnomad SAS AF: 0.566

Gnomad FIN AF: 0.378

Gnomad MID AF: 0.142

Gnomad NFE AF: 0.319

Gnomad OTH AF: 0.262

GnomAD4 exome AF: 0.345 AC: 386513 AN: 1121806 Hom.: 71820 Cov.: 15 AF XY: 0.350 AC XY: 193805 AN XY: 552996

Gnomad4 AFR exome AF: 0.152

Gnomad4 AMR exome AF: 0.313

Gnomad4 ASJ exome AF: 0.290

Gnomad4 EAS exome AF: 0.708

Gnomad4 SAS exome AF: 0.550

Gnomad4 FIN exome AF: 0.353

Gnomad4 NFE exome AF: 0.324

Gnomad4 OTH exome AF: 0.336

GnomAD4 genome AF: 0.293 AC: 44628 AN: 152082 Hom.: 7491 Cov.: 33 AF XY: 0.302 AC XY: 22451 AN XY: 74350

Gnomad4 AFR AF: 0.164

Gnomad4 AMR AF: 0.268

Gnomad4 ASJ AF: 0.286

Gnomad4 EAS AF: 0.655

Gnomad4 SAS AF: 0.567

Gnomad4 FIN AF: 0.378

Gnomad4 NFE AF: 0.319

Gnomad4 OTH AF: 0.269

Alfa AF: 0.298 Hom.: 7399

Bravo AF: 0.276

Asia WGS AF: 0.594 AC: 2061 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	12
DANN	Benign	0.73

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs2291617; hg19: chr12-58166403;