Genetic Variant NM_153265.3:c.2547C>G (chr11-62602619-G-C) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_153265.3(EML3):c.2547C>G(p.His849Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

EML3
NM_153265.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.508

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: Uncertain_significance. The variant received 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

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.2547C>G	p.His849Gln	missense	Exon 22 of 22	NP_694997.2	Q32P44-1
EML3	NM_001300793.2		c.2440C>G	p.Arg814Gly	missense	Exon 22 of 22	NP_001287722.1
EML3	NM_001300794.2		c.2437C>G	p.Arg813Gly	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.2547C>G	p.His849Gln	missense	Exon 22 of 22	ENSP00000378254.2	Q32P44-1
EML3	ENST00000964792.1		c.2658C>G	p.His886Gln	missense	Exon 23 of 23	ENSP00000634851.1
EML3	ENST00000529309.5	TSL:2	c.2437C>G	p.Arg813Gly	missense	Exon 22 of 22	ENSP00000434513.1	Q32P44-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00

AC:

AN:

190872

AF XY:

0.00

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:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1427464

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

708134

African (AFR)

AF:

0.00

AC:

AN:

32604

American (AMR)

AF:

0.00

AC:

AN:

41146

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25502

East Asian (EAS)

AF:

0.00

AC:

AN:

37898

South Asian (SAS)

AF:

0.00

AC:

AN:

82608

European-Finnish (FIN)

AF:

0.00

AC:

AN:

44532

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5724

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1098328

Other (OTH)

AF:

0.00

AC:

AN:

59122

GnomAD4 genome

Cov.:

ExAC

AF:

0.00000841

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

0.33

BayesDel_addAF

Benign

-0.090

BayesDel_noAF

Benign

-0.37

CADD

Pathogenic

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.079

Eigen

Benign

-0.023

Eigen_PC

Benign

0.023

FATHMM_MKL

Uncertain

0.81

LIST_S2

Benign

0.83

M_CAP

Uncertain

0.15

MetaRNN

Benign

0.29

MetaSVM

Benign

-1.0

MutationAssessor

Uncertain

2.2

PhyloP100

0.51

PrimateAI

Uncertain

0.74

PROVEAN

Uncertain

-3.8

REVEL

Benign

0.13

Sift

Benign

0.23

Sift4G

Benign

0.18

Polyphen

0.97

Vest4

0.40

MutPred

0.43

Loss of disorder (P = 0.1353)

MVP

0.34

MPC

1.6

ClinPred

0.94

GERP RS

3.1

Varity_R

0.24

Mutation Taster

=69/31

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.39

Details are displayed if max score is > 0.2

DS_AG_spliceai

0.39

Position offset: -1

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over