Genetic Variant EML3:p.Met834Lys (chr11-62602665-A-T) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_153265.3(EML3):c.2501T>A(p.Met834Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000346 in 1,444,816 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/19 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. M834R) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000035 ( 0 hom. )

Consequence

EML3
NM_153265.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.46

Publications

0 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:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.059341878).

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.2501T>A	p.Met834Lys	missense	Exon 22 of 22	NP_694997.2	Q32P44-1
EML3	NM_001300793.2		c.2394T>A	p.His798Gln	missense	Exon 22 of 22	NP_001287722.1
EML3	NM_001300794.2		c.2391T>A	p.His797Gln	missense	Exon 22 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.2501T>A	p.Met834Lys	missense	Exon 22 of 22	ENSP00000378254.2	Q32P44-1
EML3	ENST00000964792.1		c.2612T>A	p.Met871Lys	missense	Exon 23 of 23	ENSP00000634851.1
EML3	ENST00000529309.5	TSL:2	c.2391T>A	p.His797Gln	missense	Exon 22 of 22	ENSP00000434513.1	Q32P44-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000932

AC:

AN:

214640

AF XY:

0.0000169

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 FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000212

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000346

AC:

AN:

1444816

Hom.:

Cov.:

AF XY:

0.00000418

AC XY:

AN XY:

718068

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33164

American (AMR)

AF:

0.00

AC:

AN:

43650

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25822

East Asian (EAS)

AF:

0.00

AC:

AN:

39092

South Asian (SAS)

AF:

0.00

AC:

AN:

84828

European-Finnish (FIN)

AF:

0.00

AC:

AN:

45976

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5742

European-Non Finnish (NFE)

AF:

0.00000452

AC:

AN:

1106820

Other (OTH)

AF:

0.00

AC:

AN:

59722

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.495

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

Cov.:

ExAC

AF:

0.00000846

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.15

BayesDel_addAF

Benign

-0.075

BayesDel_noAF

Benign

-0.62

CADD

Benign

(source)

DANN

Benign

0.93

DEOGEN2

Benign

0.0066

Eigen

Benign

-0.73

Eigen_PC

Benign

-0.41

FATHMM_MKL

Benign

0.74

LIST_S2

Benign

0.35

M_CAP

Benign

0.0096

MetaRNN

Benign

0.059

MetaSVM

Benign

-0.95

PhyloP100

2.5

PROVEAN

Benign

0.31

REVEL

Benign

0.096

Sift

Pathogenic

0.0

Sift4G

Benign

0.48

Polyphen

0.0010

Vest4

0.082

MutPred

0.30

Loss of sheet (P = 0.1158)

MVP

0.12

ClinPred

0.14

GERP RS

3.8

Varity_R

0.42

gMVP

0.70

Mutation Taster

=88/12

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

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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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over