12-57780555-C-T

Position:

• chr12-57780555-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_015433.3(EEF1AKMT3):​c.590C>T​(p.Pro197Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: EEF1AKMT3 NM_015433.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.46

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 Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
EEF1AKMT3	NM_015433.3	c.590C>T	p.Pro197Leu	missense_variant	3/3	ENST00000300209.13	NP_056248.2
EEF1AKMT3	NM_206914.2	c.*279C>T		3_prime_UTR_variant	4/4		NP_996797.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
EEF1AKMT3	ENST00000300209.13	c.590C>T	p.Pro197Leu	missense_variant	3/3	1	NM_015433.3	ENSP00000300209.8
ENSG00000257921	ENST00000546504.1	c.77-2555C>T		intron_variant		2		ENSP00000449544.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Oct 25, 2024

The c.590C>T (p.P197L) alteration is located in exon 3 (coding exon 3) of the METTL21B gene. This alteration results from a C to T substitution at nucleotide position 590, causing the proline (P) at amino acid position 197 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.48
BayesDel_addAF	Benign	-0.056	T
BayesDel_noAF	Benign	-0.32
CADD	Uncertain	26
DANN	Uncertain	1.0
DEOGEN2	Benign	0.068	.;T
Eigen	Uncertain	0.52
Eigen_PC	Uncertain	0.55
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Benign	0.81	T;T
M_CAP	Benign	0.030	D
MetaRNN	Uncertain	0.44	T;T
MetaSVM	Benign	-0.95	T
PrimateAI	Uncertain	0.52	T
PROVEAN	Pathogenic	-10	D;N
REVEL	Benign	0.24
Sift	Pathogenic	0.0	D;T
Sift4G	Pathogenic	0.0	D;T
Polyphen		0.98	.;D
Vest4		0.37
MutPred		0.52		.;Loss of sheet (P = 0.0181);
MVP		0.60
MPC		1.6
ClinPred		1.0	D
GERP RS		5.2
Varity_R		0.27
gMVP		0.67

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: rs1565818185; hg19: chr12-58174338;