Variant 2-42261129-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_019063.5(EML4):c.347A>G(p.Glu116Gly) variant causes a missense change. The variant allele was found at a frequency of 0.00000206 in 1,453,590 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

EML4
NM_019063.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.04

Variant links:

Genes affected

EML4 (HGNC:1316): (EMAP like 4) This gene is a member of the echinoderm microtubule associated protein-like family. The encoded WD-repeat protein may be involved in microtubule formation. Abnormal fusion of parts of this gene with portions of the anaplastic lymphoma receptor tyrosine kinase gene, which generates EML4-ALK fusion transcripts, is one of the primary mutations associated with non-small cell lung cancer. Alternative splicing of this gene results in two transcript variants. [provided by RefSeq, Jan 2015]

EML4 links:

EML4 (HGNC:):

EML4 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.20960733).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
EML4	NM_019063.5 linkuse as main transcript	c.347A>G	p.Glu116Gly	missense_variant	4/23	ENST00000318522.10	NP_061936.3	Q9HC35-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
EML4	ENST00000318522.10 linkuse as main transcript	c.347A>G	p.Glu116Gly	missense_variant	4/23	1	NM_019063.5	ENSP00000320663.5	Q9HC35-1
EML4	ENST00000402711.6 linkuse as main transcript	c.339-2049A>G		intron_variant		1		ENSP00000385059.2	Q9HC35-2
EML4	ENST00000409040.1 linkuse as main transcript	n.578A>G		non_coding_transcript_exon_variant	4/4	1
EML4	ENST00000401738.3 linkuse as main transcript	c.347A>G	p.Glu116Gly	missense_variant	4/24	5		ENSP00000384939.3	B5MBZ0

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000206

AC:

AN:

1453590

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

723532

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

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:

0.00000271

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

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

Dec 05, 2024

The c.347A>G (p.E116G) alteration is located in exon 4 (coding exon 4) of the EML4 gene. This alteration results from a A to G substitution at nucleotide position 347, causing the glutamic acid (E) at amino acid position 116 to be replaced by a glycine (G). 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

0.097

BayesDel_addAF

Benign

-0.055

BayesDel_noAF

Benign

-0.32

CADD

Uncertain

DANN

Uncertain

0.98

DEOGEN2

Benign

0.017

T;T

Eigen

Benign

-0.15

Eigen_PC

Benign

0.015

FATHMM_MKL

Uncertain

0.96

LIST_S2

Benign

0.77

T;T

M_CAP

Benign

0.017

MetaRNN

Benign

0.21

T;T

MetaSVM

Benign

-0.98

MutationAssessor

Benign

1.7

L;.

PrimateAI

Uncertain

0.60

PROVEAN

Benign

-1.4

N;N

REVEL

Benign

0.17

Sift

Benign

0.23

T;T

Sift4G

Benign

0.27

T;T

Polyphen

0.0

B;.

Vest4

0.52

MutPred

0.22

Loss of stability (P = 0.037);Loss of stability (P = 0.037);

MVP

0.67

MPC

0.053

ClinPred

0.42

GERP RS

4.1

Varity_R

0.086

gMVP

0.22

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

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over