10-117543281-C-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_004098.4(EMX2):c.14C>T(p.Ala5Val) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000143 in 1,548,272 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. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A5P) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.000053 ( 0 hom., cov: 29)

Exomes 𝑓: 0.00015 ( 0 hom. )

Consequence

EMX2
NM_004098.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 7.65

Publications

0 publications found

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 was made for transcript

Our verdict: Benign. The variant received -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.044751137).

BS2

High AC in GnomAd4 at 8 AD,Unknown gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004098.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
EMX2	NM_004098.4	MANE Select	c.14C>T	p.Ala5Val	missense	Exon 1 of 3	NP_004089.1	Q04743-1
EMX2	NM_001165924.2		c.14C>T	p.Ala5Val	missense	Exon 1 of 2	NP_001159396.1	Q04743-2
EMX2OS	NR_002791.2		n.574+1025G>A		intron	N/A

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
EMX2	ENST00000553456.5	TSL:1 MANE Select	c.14C>T	p.Ala5Val	missense	Exon 1 of 3	ENSP00000450962.3	Q04743-1
EMX2OS	ENST00000551288.5	TSL:1	n.574+1025G>A		intron	N/A
EMX2	ENST00000442245.5	TSL:2	c.14C>T	p.Ala5Val	missense	Exon 1 of 2	ENSP00000474874.1	Q04743-2

Frequencies

GnomAD3 genomes

AF:

0.0000527

AC:

AN:

151906

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00166

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.000403

AC:

AN:

146476

AF XY:

0.000535

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000938

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000185

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000153

AC:

213

AN:

1396254

Hom.:

Cov.:

AF XY:

0.000222

AC XY:

153

AN XY:

688584

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

31400

American (AMR)

AF:

0.00

AC:

AN:

35628

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25104

East Asian (EAS)

AF:

0.0000562

AC:

AN:

35602

South Asian (SAS)

AF:

0.00249

AC:

197

AN:

79078

European-Finnish (FIN)

AF:

0.00

AC:

AN:

48022

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5458

European-Non Finnish (NFE)

AF:

0.00000464

AC:

AN:

1078106

Other (OTH)

AF:

0.000156

AC:

AN:

57856

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.513

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0000526

AC:

AN:

152018

Hom.:

Cov.:

AF XY:

0.0000942

AC XY:

AN XY:

74286

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41468

American (AMR)

AF:

0.00

AC:

AN:

15286

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3468

East Asian (EAS)

AF:

0.00

AC:

AN:

5118

South Asian (SAS)

AF:

0.00166

AC:

AN:

4812

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10584

Middle Eastern (MID)

AF:

0.00

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

67970

Other (OTH)

AF:

0.00

AC:

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.519

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0000496

Hom.:

Bravo

AF:

0.0000151

ExAC

AF:

0.000210

AC:

Asia WGS

AF:

0.00144

AC:

AN:

3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.12

BayesDel_addAF

Benign

-0.20

BayesDel_noAF

Uncertain

-0.070

CADD

Pathogenic

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.41

Eigen

Uncertain

0.29

Eigen_PC

Uncertain

0.43

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.95

M_CAP

Pathogenic

0.92

MetaRNN

Benign

0.045

MetaSVM

Uncertain

0.26

MutationAssessor

Benign

1.0

PhyloP100

7.6

PrimateAI

Pathogenic

0.80

PROVEAN

Benign

-1.8

REVEL

Uncertain

0.45

Sift

Benign

0.050

Sift4G

Uncertain

0.049

Polyphen

0.20

Vest4

0.20

MutPred

0.31

Loss of ubiquitination at A7 (P = 0.0578)

MVP

0.79

ClinPred

0.14

GERP RS

5.5

PromoterAI

-0.023

Neutral

(source)

Varity_R

0.20

gMVP

0.70

Mutation Taster

=80/20

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over