Variant 2-54725210-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001039753.4(EML6):c.149G>C(p.Arg50Pro) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000018 in 1,501,544 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00012 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000067 ( 0 hom. )

Consequence

EML6
NM_001039753.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 8.05

Variant links:

Genes affected

EML6 (HGNC:35412): (EMAP like 6) Predicted to enable microtubule binding activity. Predicted to be located in cytoplasm and microtubule. [provided by Alliance of Genome Resources, Apr 2022]

EML6 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
EML6	NM_001039753.4 linkuse as main transcript	c.149G>C	p.Arg50Pro	missense_variant	2/42	ENST00000356458.8	NP_001034842.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
EML6	ENST00000356458.8 linkuse as main transcript	c.149G>C	p.Arg50Pro	missense_variant	2/42	5	NM_001039753.4	ENSP00000348842	P1	Q6ZMW3-1
EML6	ENST00000673912.1 linkuse as main transcript	c.149G>C	p.Arg50Pro	missense_variant, NMD_transcript_variant	2/43			ENSP00000501234
EML6	ENST00000491655.1 linkuse as main transcript	n.235+540G>C		intron_variant, non_coding_transcript_variant		4

Frequencies

GnomAD3 genomes

AF:

0.000118

AC:

AN:

152056

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000411

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000655

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:

0.00

GnomAD3 exomes

AF:

0.00000885

AC:

AN:

113000

Hom.:

AF XY:

0.00

AC XY:

AN XY:

61078

show subpopulations

Gnomad AFR exome

AF:

0.000268

Gnomad AMR exome

AF:

0.00

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:

0.00000667

AC:

AN:

1349488

Hom.:

Cov.:

AF XY:

0.00000301

AC XY:

AN XY:

665418

show subpopulations

Gnomad4 AFR exome

AF:

0.000249

Gnomad4 AMR exome

AF:

0.0000330

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:

0.0000180

GnomAD4 genome

AF:

0.000118

AC:

AN:

152056

Hom.:

Cov.:

AF XY:

0.0000942

AC XY:

AN XY:

74278

show subpopulations

Gnomad4 AFR

AF:

0.000411

Gnomad4 AMR

AF:

0.0000655

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:

0.00

Bravo

AF:

0.0000831

ExAC

AF:

0.0000383

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

Mar 19, 2024

The c.149G>C (p.R50P) alteration is located in exon 1 (coding exon 1) of the EML6 gene. This alteration results from a G to C substitution at nucleotide position 149, causing the arginine (R) at amino acid position 50 to be replaced by a proline (P). 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

Pathogenic

0.98

BayesDel_addAF

Benign

-0.25

BayesDel_noAF

Benign

-0.30

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.16

Eigen

Uncertain

0.67

Eigen_PC

Pathogenic

0.67

FATHMM_MKL

Uncertain

0.95

LIST_S2

Uncertain

0.95

M_CAP

Benign

0.020

MetaRNN

Uncertain

0.53

MetaSVM

Benign

-1.2

MutationAssessor

Uncertain

2.1

MutationTaster

Benign

1.0

PrimateAI

Pathogenic

0.82

PROVEAN

Uncertain

-3.8

REVEL

Benign

0.27

Sift

Uncertain

0.028

Sift4G

Benign

0.084

Polyphen

1.0

Vest4

0.62

MVP

0.46

MPC

0.76

ClinPred

0.92

GERP RS

5.1

Varity_R

0.67

gMVP

0.62

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

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