12-57772620-T-C

Variant names:

• chr12-57772620-T-C
• rs2291617
• NM_015433.3:c.-105T>C

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_015433.3(EEF1AKMT3):​c.-105T>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000178 in 1,124,198 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 33)
  • Exomes 𝑓: 0.0000018 (0 hom.)
• Consequence: EEF1AKMT3 NM_015433.3 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.635
• Publications: 45 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).

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.-105T>C		5_prime_UTR	Exon 1 of 3	NP_056248.2
	EEF1AKMT3	NM_206914.2		c.-105T>C		5_prime_UTR	Exon 1 of 4	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.-105T>C		5_prime_UTR	Exon 1 of 3	ENSP00000300209.8	Q96AZ1-1
	EEF1AKMT3	ENST00000548256.5	TSL:4	c.52-397T>C		intron	N/A	ENSP00000447718.1	F8VZI8
	EEF1AKMT3	ENST00000551420.1	TSL:2	c.-367+223T>C		intron	N/A	ENSP00000448163.1	F8W226

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000178 AC: 2 AN: 1124198 Hom.: 0 Cov.: 15 AF XY: 0.00000180 AC XY: 1 AN XY: 554200

African (AFR) AF: 0.00 AC: 0 AN: 25018

American (AMR) AF: 0.00 AC: 0 AN: 21818

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 18230

East Asian (EAS) AF: 0.00 AC: 0 AN: 33880

South Asian (SAS) AF: 0.00 AC: 0 AN: 61770

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 38042

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3356

European-Non Finnish (NFE) AF: 0.00000229 AC: 2 AN: 874014

Other (OTH) AF: 0.00 AC: 0 AN: 48070

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 9865

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	12
DANN	Benign	0.78
PhyloP100		0.64
PromoterAI		-0.018	Neutral

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs2291617; hg19: chr12-58166403;