dbSNP rs774505119: EML3:p.Met834Arg (chr11-62602665-A-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.2501T>G(p.Met834Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000167 in 1,597,124 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. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00011 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00017 ( 0 hom. )

Consequence

EML3
NM_153265.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

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:

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=0.059236676).

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>G	p.Met834Arg	missense	Exon 22 of 22	NP_694997.2	Q32P44-1
EML3	NM_001300793.2		c.2394T>G	p.His798Gln	missense	Exon 22 of 22	NP_001287722.1
EML3	NM_001300794.2		c.2391T>G	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>G	p.Met834Arg	missense	Exon 22 of 22	ENSP00000378254.2	Q32P44-1
EML3	ENST00000964792.1		c.2612T>G	p.Met871Arg	missense	Exon 23 of 23	ENSP00000634851.1
EML3	ENST00000529309.5	TSL:2	c.2391T>G	p.His797Gln	missense	Exon 22 of 22	ENSP00000434513.1	Q32P44-2

Frequencies

GnomAD3 genomes

AF:

0.000112

AC:

AN:

152190

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000483

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000654

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:

0.000206

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000466

AC:

AN:

214640

AF XY:

0.0000591

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:

0.000106

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000172

AC:

249

AN:

1444816

Hom.:

Cov.:

AF XY:

0.000143

AC XY:

103

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:

0.000174

AC:

AN:

5742

European-Non Finnish (NFE)

AF:

0.000220

AC:

243

AN:

1106820

Other (OTH)

AF:

0.0000837

AC:

AN:

59722

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.509

Heterozygous variant carriers

118

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:

0.000112

AC:

AN:

152308

Hom.:

Cov.:

AF XY:

0.000134

AC XY:

AN XY:

74482

show subpopulations

African (AFR)

AF:

0.0000481

AC:

AN:

41572

American (AMR)

AF:

0.0000653

AC:

AN:

15308

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5166

South Asian (SAS)

AF:

0.00

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10624

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000206

AC:

AN:

68016

Other (OTH)

AF:

0.00

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

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:

0.000136

Hom.:

Bravo

AF:

0.0000718

ExAC

AF:

0.0000423

AC:

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

0.15

BayesDel_addAF

Benign

-0.21

BayesDel_noAF

Benign

-0.52

CADD

Benign

(source)

DANN

Benign

0.92

DEOGEN2

Benign

0.0066

Eigen

Benign

-0.49

Eigen_PC

Benign

-0.23

FATHMM_MKL

Uncertain

0.87

LIST_S2

Benign

0.35

M_CAP

Benign

0.018

MetaRNN

Benign

0.059

MetaSVM

Benign

-1.0

PhyloP100

2.5

PROVEAN

Benign

0.31

REVEL

Benign

0.095

Sift

Pathogenic

0.0

Sift4G

Benign

0.48

Polyphen

0.0010

Vest4

0.082

MutPred

0.30

Loss of sheet (P = 0.1158)

MVP

0.17

ClinPred

0.097

GERP RS

3.8

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.48

gMVP

0.70

Mutation Taster

=80/20

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

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