Variant 11-62602481-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_153265.3(EML3):c.2685C>A(p.Asp895Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000683 in 1,536,534 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00035 ( 1 hom., cov: 33)

Exomes 𝑓: 0.000038 ( 0 hom. )

Consequence

EML3
NM_153265.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.786

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 made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.032463133).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
EML3	NM_153265.3 linkuse as main transcript	c.2685C>A	p.Asp895Glu	missense_variant	22/22	ENST00000394773.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
EML3	ENST00000394773.7 linkuse as main transcript	c.2685C>A	p.Asp895Glu	missense_variant	22/22	1	NM_153265.3	P4	Q32P44-1

Frequencies

GnomAD3 genomes

AF:

0.000348

AC:

AN:

152180

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00106

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000458

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:

0.00

Gnomad OTH

AF:

0.000958

GnomAD3 exomes

AF:

0.0000797

AC:

AN:

138056

Hom.:

AF XY:

0.0000536

AC XY:

AN XY:

74652

show subpopulations

Gnomad AFR exome

AF:

0.00129

Gnomad AMR exome

AF:

0.000133

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000376

AC:

AN:

1384354

Hom.:

Cov.:

AF XY:

0.0000337

AC XY:

AN XY:

681924

show subpopulations

Gnomad4 AFR exome

AF:

0.00117

Gnomad4 AMR exome

AF:

0.000118

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.000209

GnomAD4 genome

AF:

0.000348

AC:

AN:

152180

Hom.:

Cov.:

AF XY:

0.000363

AC XY:

AN XY:

74336

show subpopulations

Gnomad4 AFR

AF:

0.00106

Gnomad4 AMR

AF:

0.000458

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.000958

Alfa

AF:

0.000139

Hom.:

Bravo

AF:

0.000438

ExAC

AF:

0.0000273

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

May 15, 2024

The c.2685C>A (p.D895E) alteration is located in exon 22 (coding exon 22) of the EML3 gene. This alteration results from a C to A substitution at nucleotide position 2685, causing the aspartic acid (D) at amino acid position 895 to be replaced by a glutamic acid (E). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.15

BayesDel_addAF

Benign

-0.57

BayesDel_noAF

Benign

-0.63

CADD

Benign

DANN

Benign

0.77

DEOGEN2

Benign

0.0075

T;T;.;T

Eigen

Benign

-0.40

Eigen_PC

Benign

-0.38

FATHMM_MKL

Benign

0.48

LIST_S2

Benign

0.57

T;T;T;T

M_CAP

Benign

0.078

MetaRNN

Benign

0.032

T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.0

.;N;.;.

MutationTaster

Benign

1.0

N;N;N;N;N

PrimateAI

Pathogenic

0.84

PROVEAN

Benign

-0.29

N;N;N;N

REVEL

Benign

0.075

Sift

Benign

0.70

T;T;T;T

Sift4G

Pathogenic

0.0

D;T;T;T

Polyphen

0.80, 0.63

.;P;P;P

Vest4

0.068, 0.079, 0.067

MutPred

0.14

.;.;Gain of glycosylation at P891 (P = 0.1298);.;

MVP

0.27

MPC

0.65

ClinPred

0.025

GERP RS

0.77

Varity_R

0.046

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.060

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over