12-57780523-T-C

Variant names:

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

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_015433.3(EEF1AKMT3):​c.558T>C​(p.His186His) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.345 in 1,613,716 control chromosomes in the GnomAD database, including 102,977 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 0.31 (8111 hom., cov: 32)
  • Exomes 𝑓: 0.35 (94866 hom.)
• Consequence: EEF1AKMT3 NM_015433.3 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.46

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

Verdict is Benign. Variant got -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BP7: Synonymous conserved (PhyloP=-1.46 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.638 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EEF1AKMT3	NM_015433.3	c.558T>C	p.His186His	synonymous_variant	Exon 3 of 3	ENST00000300209.13	NP_056248.2
EEF1AKMT3	NM_206914.2	c.*247T>C		3_prime_UTR_variant	Exon 4 of 4		NP_996797.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EEF1AKMT3	ENST00000300209.13	c.558T>C	p.His186His	synonymous_variant	Exon 3 of 3	1	NM_015433.3	ENSP00000300209.8
ENSG00000257921	ENST00000546504.1	c.77-2587T>C		intron_variant	Intron 1 of 3	2		ENSP00000449544.1

Frequencies

GnomAD3 genomes AF: 0.312 AC: 47458 AN: 152022 Hom.: 8085 Cov.: 32

Gnomad AFR AF: 0.230

Gnomad AMI AF: 0.381

Gnomad AMR AF: 0.273

Gnomad ASJ AF: 0.286

Gnomad EAS AF: 0.656

Gnomad SAS AF: 0.565

Gnomad FIN AF: 0.379

Gnomad MID AF: 0.152

Gnomad NFE AF: 0.319

Gnomad OTH AF: 0.267

GnomAD3 exomes AF: 0.376 AC: 94268 AN: 250734 Hom.: 19562 AF XY: 0.384 AC XY: 52082 AN XY: 135552

Gnomad AFR exome AF: 0.230

Gnomad AMR exome AF: 0.357

Gnomad ASJ exome AF: 0.276

Gnomad EAS exome AF: 0.635

Gnomad SAS exome AF: 0.561

Gnomad FIN exome AF: 0.364

Gnomad NFE exome AF: 0.325

Gnomad OTH exome AF: 0.324

GnomAD4 exome AF: 0.349 AC: 509867 AN: 1461576 Hom.: 94866 Cov.: 62 AF XY: 0.355 AC XY: 257828 AN XY: 727060

Gnomad4 AFR exome AF: 0.218

Gnomad4 AMR exome AF: 0.347

Gnomad4 ASJ exome AF: 0.288

Gnomad4 EAS exome AF: 0.701

Gnomad4 SAS exome AF: 0.551

Gnomad4 FIN exome AF: 0.357

Gnomad4 NFE exome AF: 0.327

Gnomad4 OTH exome AF: 0.341

GnomAD4 genome AF: 0.312 AC: 47534 AN: 152140 Hom.: 8111 Cov.: 32 AF XY: 0.321 AC XY: 23836 AN XY: 74342

Gnomad4 AFR AF: 0.231

Gnomad4 AMR AF: 0.273

Gnomad4 ASJ AF: 0.286

Gnomad4 EAS AF: 0.656

Gnomad4 SAS AF: 0.567

Gnomad4 FIN AF: 0.379

Gnomad4 NFE AF: 0.319

Gnomad4 OTH AF: 0.273

Alfa AF: 0.306 Hom.: 5513

Bravo AF: 0.297

Asia WGS AF: 0.601 AC: 2088 AN: 3478

EpiCase AF: 0.306

EpiControl AF: 0.299

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	1.0
DANN	Benign	0.58

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: rs923829; hg19: chr12-58174306;