Genetic Variant EEF1AKMT3:c.-105T>G (chr12-57772620-T-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_015433.3(EEF1AKMT3):c.-105T>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.338 in 1,273,888 control chromosomes in the GnomAD database, including 79,311 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 0.29 ( 7491 hom., cov: 33)

Exomes 𝑓: 0.34 ( 71820 hom. )

Consequence

EEF1AKMT3
NM_015433.3 5_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.635

Publications

45 publications found

Variant links:

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]

EEF1AKMT3 links:

ENSG00000257921 (HGNC:):

ENSG00000257921 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.83).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.636 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EEF1AKMT3	NM_015433.3 link	c.-105T>G		5_prime_UTR_variant	Exon 1 of 3	ENST00000300209.13	NP_056248.2
EEF1AKMT3	NM_206914.2 link	c.-105T>G		5_prime_UTR_variant	Exon 1 of 4		NP_996797.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EEF1AKMT3	ENST00000300209.13 link	c.-105T>G		5_prime_UTR_variant	Exon 1 of 3	1	NM_015433.3	ENSP00000300209.8		Q96AZ1-1

Frequencies

GnomAD3 genomes

AF:

0.293

AC:

44579

AN:

151964

Hom.:

7472

Cov.:

show subpopulations

Gnomad AFR

AF:

0.164

Gnomad AMI

AF:

0.384

Gnomad AMR

AF:

0.268

Gnomad ASJ

AF:

0.286

Gnomad EAS

AF:

0.655

Gnomad SAS

AF:

0.566

Gnomad FIN

AF:

0.378

Gnomad MID

AF:

0.142

Gnomad NFE

AF:

0.319

Gnomad OTH

AF:

0.262

GnomAD4 exome

AF:

0.345

AC:

386513

AN:

1121806

Hom.:

71820

Cov.:

AF XY:

0.350

AC XY:

193805

AN XY:

552996

show subpopulations

African (AFR)

AF:

0.152

AC:

3786

AN:

24982

American (AMR)

AF:

0.313

AC:

6819

AN:

21794

Ashkenazi Jewish (ASJ)

AF:

0.290

AC:

5283

AN:

18218

East Asian (EAS)

AF:

0.708

AC:

23964

AN:

33842

South Asian (SAS)

AF:

0.550

AC:

33923

AN:

61660

European-Finnish (FIN)

AF:

0.353

AC:

13398

AN:

37996

Middle Eastern (MID)

AF:

0.222

AC:

743

AN:

3348

European-Non Finnish (NFE)

AF:

0.324

AC:

282461

AN:

871968

Other (OTH)

AF:

0.336

AC:

16136

AN:

47998

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

11898

23796

35693

47591

59489

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

9138

18276

27414

36552

45690

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.293

AC:

44628

AN:

152082

Hom.:

7491

Cov.:

AF XY:

0.302

AC XY:

22451

AN XY:

74350

show subpopulations

African (AFR)

AF:

0.164

AC:

6796

AN:

41514

American (AMR)

AF:

0.268

AC:

4099

AN:

15298

Ashkenazi Jewish (ASJ)

AF:

0.286

AC:

992

AN:

3470

East Asian (EAS)

AF:

0.655

AC:

3370

AN:

5148

South Asian (SAS)

AF:

0.567

AC:

2736

AN:

4826

European-Finnish (FIN)

AF:

0.378

AC:

3998

AN:

10582

Middle Eastern (MID)

AF:

0.150

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.319

AC:

21678

AN:

67934

Other (OTH)

AF:

0.269

AC:

566

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.508

Heterozygous variant carriers

1605

3210

4814

6419

8024

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

472

944

1416

1888

2360

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.301

Hom.:

9865

Bravo

AF:

0.276

Asia WGS

AF:

0.594

AC:

2061

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

CADD

Benign

(source)

DANN

Benign

0.73

PhyloP100

0.64

PromoterAI

-0.12

Neutral

(source)

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over