Variant 10-124791749-G-A details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_212554.4(EEF1AKMT2):c.85C>T(p.Pro29Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000208 in 1,440,914 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

EEF1AKMT2
NM_212554.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.26

Variant links:

Genes affected

EEF1AKMT2 (HGNC:33787): (EEF1A lysine methyltransferase 2) Enables protein-lysine N-methyltransferase activity. Involved in peptidyl-lysine methylation. Located in cytosol and nuclear body. [provided by Alliance of Genome Resources, Apr 2022]

EEF1AKMT2 links:

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ACMG classification

Classification made for transcript

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
EEF1AKMT2	NM_212554.4 linkuse as main transcript	c.85C>T	p.Pro29Ser	missense_variant	1/7	ENST00000368836.7
EEF1AKMT2	NM_001416243.1 linkuse as main transcript	c.85C>T	p.Pro29Ser	missense_variant	1/6
EEF1AKMT2	NM_001304467.2 linkuse as main transcript	c.-154C>T		5_prime_UTR_variant	1/7
EEF1AKMT2	NM_001304468.2 linkuse as main transcript	c.-154C>T		5_prime_UTR_variant	1/6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
EEF1AKMT2	ENST00000368836.7 linkuse as main transcript	c.85C>T	p.Pro29Ser	missense_variant	1/7	1	NM_212554.4
EEF1AKMT2	ENST00000464099.5 linkuse as main transcript	c.85C>T	p.Pro29Ser	missense_variant, NMD_transcript_variant	1/6	1
EEF1AKMT2	ENST00000466270.5 linkuse as main transcript	c.85C>T	p.Pro29Ser	missense_variant, NMD_transcript_variant	1/7	1
EEF1AKMT2	ENST00000652548.2 linkuse as main transcript	c.85C>T	p.Pro29Ser	missense_variant	1/6			P1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000479

AC:

AN:

208682

Hom.:

AF XY:

0.00000870

AC XY:

AN XY:

115004

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000358

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000208

AC:

AN:

1440914

Hom.:

Cov.:

AF XY:

0.00000279

AC XY:

AN XY:

715950

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000119

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000181

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.0000113

ExAC

AF:

0.00000836

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 14, 2023

The c.85C>T (p.P29S) alteration is located in exon 1 (coding exon 1) of the METTL10 gene. This alteration results from a C to T substitution at nucleotide position 85, causing the proline (P) at amino acid position 29 to be replaced by a serine (S). 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

0.16

BayesDel_addAF

Benign

-0.089

BayesDel_noAF

Benign

-0.37

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.047

Eigen

Benign

0.074

Eigen_PC

Benign

-0.0077

FATHMM_MKL

Benign

0.039

LIST_S2

Uncertain

0.86

M_CAP

Benign

0.031

MetaRNN

Uncertain

0.48

MetaSVM

Benign

-0.92

PrimateAI

Uncertain

0.70

PROVEAN

Uncertain

-3.0

REVEL

Benign

0.12

Sift

Benign

0.098

Sift4G

Benign

0.12

Polyphen

1.0

Vest4

0.55

MutPred

0.32

Loss of helix (P = 0.0626);

MVP

0.31

MPC

0.13

ClinPred

0.96

GERP RS

3.5

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.18

gMVP

0.54

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over