12-57780456-G-C

Position:

• chr12-57780456-G-C

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_015433.3(EEF1AKMT3):​c.491G>C​(p.Gly164Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict 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: 32)
• Consequence: EEF1AKMT3 NM_015433.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.64

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 Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.06797409).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
EEF1AKMT3	NM_015433.3	c.491G>C	p.Gly164Ala	missense_variant	3/3	ENST00000300209.13	NP_056248.2
EEF1AKMT3	NM_206914.2	c.*180G>C		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.491G>C	p.Gly164Ala	missense_variant	3/3	1	NM_015433.3	ENSP00000300209.8
ENSG00000257921	ENST00000546504.1	c.77-2654G>C		intron_variant		2		ENSP00000449544.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

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

Nov 25, 2024

The c.491G>C (p.G164A) alteration is located in exon 3 (coding exon 3) of the METTL21B gene. This alteration results from a G to C substitution at nucleotide position 491, causing the glycine (G) at amino acid position 164 to be replaced by an alanine (A). 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	Benign	0.11
BayesDel_addAF	Benign	-0.32	T
BayesDel_noAF	Benign	-0.70
CADD	Benign	21
DANN	Uncertain	0.98
DEOGEN2	Benign	0.00090	T
Eigen	Benign	-0.42
Eigen_PC	Benign	-0.14
FATHMM_MKL	Uncertain	0.86	D
LIST_S2	Benign	0.78	T
M_CAP	Benign	0.0091	T
MetaRNN	Benign	0.068	T
MetaSVM	Benign	-0.89	T
PrimateAI	Uncertain	0.62	T
PROVEAN	Benign	1.0	N
REVEL	Benign	0.056
Sift	Benign	0.75	T
Sift4G	Benign	0.71	T
Polyphen		0.0010	B
Vest4		0.074
MutPred		0.41		Loss of catalytic residue at P160 (P = 0.0885);
MVP		0.14
MPC		0.74
ClinPred		0.10	T
GERP RS		4.3
Varity_R		0.095
gMVP		0.43

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr12-58174239;