Genetic Variant EML3:p.Ile563Val (chr11-62605950-T-C) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_153265.3(EML3):c.1687A>G(p.Ile563Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000128 in 1,614,056 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00012 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00013 ( 0 hom. )

Consequence

EML3
NM_153265.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.701

Publications

1 publications found

Variant links:

Genes affected

EML3 (HGNC:26666): (EMAP like 3) Predicted to enable microtubule binding activity. Involved in mitotic metaphase plate congression and regulation of mitotic spindle assembly. Located in several cellular components, including midbody; mitotic spindle microtubule; and nucleus. [provided by Alliance of Genome Resources, Apr 2022]

EML3 links:

ENSG00000254964 (HGNC:):

ENSG00000254964 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.049610764).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_153265.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
EML3	NM_153265.3	MANE Select	c.1687A>G	p.Ile563Val	missense	Exon 14 of 22	NP_694997.2	Q32P44-1
EML3	NM_001300793.2		c.1690A>G	p.Ile564Val	missense	Exon 14 of 22	NP_001287722.1
EML3	NM_001300794.2		c.1687A>G	p.Ile563Val	missense	Exon 14 of 22	NP_001287723.1	Q32P44-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
EML3	ENST00000394773.7	TSL:1 MANE Select	c.1687A>G	p.Ile563Val	missense	Exon 14 of 22	ENSP00000378254.2	Q32P44-1
EML3	ENST00000964792.1		c.1798A>G	p.Ile600Val	missense	Exon 15 of 23	ENSP00000634851.1
EML3	ENST00000529309.5	TSL:2	c.1687A>G	p.Ile563Val	missense	Exon 14 of 22	ENSP00000434513.1	Q32P44-2

Frequencies

GnomAD3 genomes

AF:

0.000125

AC:

AN:

152208

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000279

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.000163

AC:

AN:

251240

AF XY:

0.000199

show subpopulations

Gnomad AFR exome

AF:

0.000123

Gnomad AMR exome

AF:

0.000116

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000299

Gnomad OTH exome

AF:

0.000163

GnomAD4 exome

AF:

0.000129

AC:

188

AN:

1461848

Hom.:

Cov.:

AF XY:

0.000132

AC XY:

AN XY:

727228

show subpopulations

African (AFR)

AF:

0.0000896

AC:

AN:

33478

American (AMR)

AF:

0.000179

AC:

AN:

44722

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26134

East Asian (EAS)

AF:

0.00

AC:

AN:

39700

South Asian (SAS)

AF:

0.00

AC:

AN:

86258

European-Finnish (FIN)

AF:

0.0000187

AC:

AN:

53384

Middle Eastern (MID)

AF:

0.000173

AC:

AN:

5766

European-Non Finnish (NFE)

AF:

0.000153

AC:

170

AN:

1112010

Other (OTH)

AF:

0.0000828

AC:

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.493

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<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:

0.000125

AC:

AN:

152208

Hom.:

Cov.:

AF XY:

0.000134

AC XY:

AN XY:

74356

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41452

American (AMR)

AF:

0.00

AC:

AN:

15286

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5200

South Asian (SAS)

AF:

0.00

AC:

AN:

4832

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10620

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.000279

AC:

AN:

68028

Other (OTH)

AF:

0.00

AC:

AN:

2090

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<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:

0.000270

Hom.:

Bravo

AF:

0.000121

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.000259

AC:

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.000233

AC:

ExAC

AF:

0.000123

AC:

EpiCase

AF:

0.000545

EpiControl

AF:

0.000652

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.099

BayesDel_addAF

Benign

-0.44

BayesDel_noAF

Benign

-0.51

CADD

Benign

(source)

DANN

Benign

0.76

DEOGEN2

Benign

0.012

Eigen

Benign

-0.51

Eigen_PC

Benign

-0.25

FATHMM_MKL

Uncertain

0.86

LIST_S2

Benign

0.84

M_CAP

Benign

0.0057

MetaRNN

Benign

0.050

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-0.72

PhyloP100

0.70

PrimateAI

Uncertain

0.52

PROVEAN

Benign

0.12

REVEL

Benign

0.10

Sift

Benign

1.0

Sift4G

Benign

1.0

Polyphen

0.0060

Vest4

0.23

MVP

0.19

MPC

0.63

ClinPred

0.019

GERP RS

5.3

Varity_R

0.043

gMVP

0.22

Mutation Taster

=84/16

polymorphism

(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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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