dbSNP rs1327726416: EML3:p.Ala875Thr (chr11-62602543-C-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.2623G>A(p.Ala875Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000302 in 1,487,866 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000079 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000025 ( 0 hom. )

Consequence

EML3
NM_153265.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.469

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 -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.05342239).

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.2623G>A	p.Ala875Thr	missense	Exon 22 of 22	NP_694997.2	Q32P44-1
EML3	NM_001300793.2		c.2516G>A	p.Arg839His	missense	Exon 22 of 22	NP_001287722.1
EML3	NM_001300794.2		c.2513G>A	p.Arg838His	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.2623G>A	p.Ala875Thr	missense	Exon 22 of 22	ENSP00000378254.2	Q32P44-1
EML3	ENST00000964792.1		c.2734G>A	p.Ala912Thr	missense	Exon 23 of 23	ENSP00000634851.1
EML3	ENST00000529309.5	TSL:2	c.2513G>A	p.Arg838His	missense	Exon 22 of 22	ENSP00000434513.1	Q32P44-2

Frequencies

GnomAD3 genomes

AF:

0.0000788

AC:

AN:

152230

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000482

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:

0.000147

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000118

AC:

AN:

85000

AF XY:

0.0000221

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:

0.0000332

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000247

AC:

AN:

1335636

Hom.:

Cov.:

AF XY:

0.0000184

AC XY:

AN XY:

653940

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

29222

American (AMR)

AF:

0.00

AC:

AN:

26628

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

20932

East Asian (EAS)

AF:

0.00

AC:

AN:

34896

South Asian (SAS)

AF:

0.00

AC:

AN:

68940

European-Finnish (FIN)

AF:

0.00

AC:

AN:

41846

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5278

European-Non Finnish (NFE)

AF:

0.0000295

AC:

AN:

1052480

Other (OTH)

AF:

0.0000361

AC:

AN:

55414

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

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:

0.0000788

AC:

AN:

152230

Hom.:

Cov.:

AF XY:

0.0000807

AC XY:

AN XY:

74368

show subpopulations

African (AFR)

AF:

0.0000482

AC:

AN:

41460

American (AMR)

AF:

0.00

AC:

AN:

15286

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5200

South Asian (SAS)

AF:

0.00

AC:

AN:

4836

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10626

Middle Eastern (MID)

AF:

0.00

AC:

AN:

314

European-Non Finnish (NFE)

AF:

0.000147

AC:

AN:

68032

Other (OTH)

AF:

0.00

AC:

AN:

2094

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.467

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:

0.00

Hom.:

Bravo

AF:

0.0000604

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

0.072

BayesDel_addAF

Benign

-0.39

BayesDel_noAF

Benign

-0.69

CADD

Benign

(source)

DANN

Benign

0.94

DEOGEN2

Benign

0.0090

Eigen

Benign

-0.80

Eigen_PC

Benign

-0.72

FATHMM_MKL

Benign

0.12

LIST_S2

Benign

0.66

M_CAP

Benign

0.013

MetaRNN

Benign

0.053

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.0

PhyloP100

-0.47

PrimateAI

Uncertain

0.61

PROVEAN

Benign

-0.40

REVEL

Benign

0.069

Sift

Benign

0.36

Sift4G

Benign

0.35

Polyphen

0.0

Vest4

0.039

MutPred

0.23

Gain of glycosylation at A876 (P = 0.0301)

MVP

0.17

MPC

0.68

ClinPred

0.10

GERP RS

-0.51

Varity_R

0.054

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

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