Variant 10-117543615-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_StrongBP7BS2

The NM_004098.4(EMX2):c.348G>T(p.Pro116=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00023 in 1,612,754 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00017 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00024 ( 0 hom. )

Consequence

EMX2
NM_004098.4 synonymous

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.254

Variant links:

Genes affected

EMX2 (HGNC:3341): (empty spiracles homeobox 2) This gene encodes a homeobox-containing transcription factor that is the homolog to the 'empty spiracles' gene in Drosophila. Research on this gene in humans has focused on its expression in three tissues: dorsal telencephalon, olfactory neuroepithelium, and urogenetial system. It is expressed in the dorsal telencephalon during development in a low rostral-lateral to high caudal-medial gradient and is proposed to pattern the neocortex into defined functional areas. It is also expressed in embryonic and adult olfactory neuroepithelia where it complexes with eukaryotic translation initiation factor 4E (eIF4E) and possibly regulates mRNA transport or translation. In the developing urogenital system, it is expressed in epithelial tissues and is negatively regulated by HOXA10. Alternative splicing results in multiple transcript variants encoding distinct proteins.[provided by RefSeq, Sep 2009]

EMX2 links:

EMX2OS (HGNC:18511): (EMX2 opposite strand/antisense RNA)

EMX2OS links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -9 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.54).

BP7

Synonymous conserved (PhyloP=-0.254 with no splicing effect.

BS2

High AC in GnomAd4 at 26 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
EMX2	NM_004098.4 linkuse as main transcript	c.348G>T	p.Pro116=	synonymous_variant	1/3	ENST00000553456.5	NP_004089.1
EMX2OS	NR_002791.2 linkuse as main transcript	n.574+691C>A		intron_variant, non_coding_transcript_variant
EMX2	NM_001165924.2 linkuse as main transcript	c.348G>T	p.Pro116=	synonymous_variant	1/2		NP_001159396.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
EMX2	ENST00000553456.5 linkuse as main transcript	c.348G>T	p.Pro116=	synonymous_variant	1/3	1	NM_004098.4	ENSP00000450962	P1	Q04743-1
EMX2OS	ENST00000551288.5 linkuse as main transcript	n.574+691C>A		intron_variant, non_coding_transcript_variant		1
EMX2	ENST00000442245.5 linkuse as main transcript	c.348G>T	p.Pro116=	synonymous_variant	1/2	2		ENSP00000474874		Q04743-2
EMX2	ENST00000616794.1 linkuse as main transcript	c.48G>T	p.Pro16=	synonymous_variant	1/2	2		ENSP00000480271

Frequencies

GnomAD3 genomes

AF:

0.000172

AC:

AN:

151492

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000243

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000197

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:

0.000309

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.000132

AC:

AN:

250102

Hom.:

AF XY:

0.000155

AC XY:

AN XY:

135406

show subpopulations

Gnomad AFR exome

AF:

0.0000617

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000327

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000275

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000236

AC:

345

AN:

1461262

Hom.:

Cov.:

AF XY:

0.000238

AC XY:

173

AN XY:

726994

show subpopulations

Gnomad4 AFR exome

AF:

0.0000897

Gnomad4 AMR exome

AF:

0.0000224

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000116

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000299

Gnomad4 OTH exome

AF:

0.000116

GnomAD4 genome

AF:

0.000172

AC:

AN:

151492

Hom.:

Cov.:

AF XY:

0.000216

AC XY:

AN XY:

73944

show subpopulations

Gnomad4 AFR

AF:

0.0000243

Gnomad4 AMR

AF:

0.000197

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000309

Gnomad4 OTH

AF:

0.000478

Alfa

AF:

0.000259

Hom.:

Bravo

AF:

0.000185

EpiCase

AF:

0.000164

EpiControl

AF:

0.000178

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Eurofins Ntd Llc (ga)

May 23, 2017

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.54

CADD

Benign

DANN

Benign

0.89

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