Genetic Variant EEF1AKMT3:p.His186His (chr12-57780523-T-C) – ACMG Classification: Benign (-13 pts)

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_StrongBP7BA1

The NM_015433.3(EEF1AKMT3):c.558T>C(p.His186His) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.345 in 1,613,716 control chromosomes in the GnomAD database, including 102,977 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 0.31 ( 8111 hom., cov: 32)

Exomes 𝑓: 0.35 ( 94866 hom. )

Consequence

EEF1AKMT3
NM_015433.3 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.46

Publications

44 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 -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.84).

BP7

Synonymous conserved (PhyloP=-1.46 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.638 is higher than 0.05.

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.558T>C	p.His186His	synonymous	Exon 3 of 3	NP_056248.2
	EEF1AKMT3	NM_206914.2		c.*247T>C		3_prime_UTR	Exon 4 of 4	NP_996797.1	Q96AZ1-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
EEF1AKMT3	ENST00000300209.13	TSL:1 MANE Select	c.558T>C	p.His186His	synonymous	Exon 3 of 3	ENSP00000300209.8	Q96AZ1-1
EEF1AKMT3	ENST00000333012.5	TSL:1	c.*247T>C		3_prime_UTR	Exon 4 of 4	ENSP00000327425.5	Q96AZ1-2
ENSG00000257921	ENST00000546504.1	TSL:2	c.77-2587T>C		intron	N/A	ENSP00000449544.1	H0YIJ7

Frequencies

GnomAD3 genomes

AF:

0.312

AC:

47458

AN:

152022

Hom.:

8085

Cov.:

show subpopulations

Gnomad AFR

AF:

0.230

Gnomad AMI

AF:

0.381

Gnomad AMR

AF:

0.273

Gnomad ASJ

AF:

0.286

Gnomad EAS

AF:

0.656

Gnomad SAS

AF:

0.565

Gnomad FIN

AF:

0.379

Gnomad MID

AF:

0.152

Gnomad NFE

AF:

0.319

Gnomad OTH

AF:

0.267

GnomAD2 exomes

AF:

0.376

AC:

94268

AN:

250734

AF XY:

0.384

show subpopulations

Gnomad AFR exome

AF:

0.230

Gnomad AMR exome

AF:

0.357

Gnomad ASJ exome

AF:

0.276

Gnomad EAS exome

AF:

0.635

Gnomad FIN exome

AF:

0.364

Gnomad NFE exome

AF:

0.325

Gnomad OTH exome

AF:

0.324

GnomAD4 exome

AF:

0.349

AC:

509867

AN:

1461576

Hom.:

94866

Cov.:

AF XY:

0.355

AC XY:

257828

AN XY:

727060

show subpopulations

African (AFR)

AF:

0.218

AC:

7288

AN:

33480

American (AMR)

AF:

0.347

AC:

15476

AN:

44646

Ashkenazi Jewish (ASJ)

AF:

0.288

AC:

7525

AN:

26132

East Asian (EAS)

AF:

0.701

AC:

27849

AN:

39700

South Asian (SAS)

AF:

0.551

AC:

47567

AN:

86252

European-Finnish (FIN)

AF:

0.357

AC:

19073

AN:

53368

Middle Eastern (MID)

AF:

0.208

AC:

1199

AN:

5768

European-Non Finnish (NFE)

AF:

0.327

AC:

363276

AN:

1111844

Other (OTH)

AF:

0.341

AC:

20614

AN:

60386

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.482

Heterozygous variant carriers

22227

44454

66682

88909

111136

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

12030

24060

36090

48120

60150

<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:

0.312

AC:

47534

AN:

152140

Hom.:

8111

Cov.:

AF XY:

0.321

AC XY:

23836

AN XY:

74342

show subpopulations

African (AFR)

AF:

0.231

AC:

9573

AN:

41530

American (AMR)

AF:

0.273

AC:

4181

AN:

15294

Ashkenazi Jewish (ASJ)

AF:

0.286

AC:

991

AN:

3470

East Asian (EAS)

AF:

0.656

AC:

3391

AN:

5166

South Asian (SAS)

AF:

0.567

AC:

2732

AN:

4822

European-Finnish (FIN)

AF:

0.379

AC:

4009

AN:

10584

Middle Eastern (MID)

AF:

0.160

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.319

AC:

21689

AN:

67962

Other (OTH)

AF:

0.273

AC:

576

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1627

3254

4880

6507

8134

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

496

992

1488

1984

2480

<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:

0.302

Hom.:

6009

Bravo

AF:

0.297

Asia WGS

AF:

0.601

AC:

2088

AN:

3478

EpiCase

AF:

0.306

EpiControl

AF:

0.299

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

CADD

Benign

1.0

(source)

DANN

Benign

0.58

PhyloP100

-1.5

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over