10-117543388-T-G

Position:

chr10-117543388-T-G

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_ModerateBP6_ModerateBS2

The NM_004098.4(EMX2):c.121T>G(p.Ser41Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000424 in 1,580,974 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00018 ( 0 hom., cov: 29)

Exomes 𝑓: 0.000027 ( 0 hom. )

Consequence

EMX2
NM_004098.4 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.93

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:):

EMX2OS links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.109916896).

BP6

Variant 10-117543388-T-G is Benign according to our data. Variant chr10-117543388-T-G is described in ClinVar as [Likely_benign]. Clinvar id is 2266545.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High AC in GnomAd4 at 28 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
EMX2	NM_004098.4 linkuse as main transcript	c.121T>G	p.Ser41Ala	missense_variant	1/3	ENST00000553456.5	NP_004089.1	Q04743-1
EMX2	NM_001165924.2 linkuse as main transcript	c.121T>G	p.Ser41Ala	missense_variant	1/2		NP_001159396.1	Q04743-2
EMX2OS	NR_002791.2 linkuse as main transcript	n.574+918A>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
EMX2	ENST00000553456.5 linkuse as main transcript	c.121T>G	p.Ser41Ala	missense_variant	1/3	1	NM_004098.4	ENSP00000450962.3	Q04743-1
EMX2OS	ENST00000551288.5 linkuse as main transcript	n.574+918A>C		intron_variant		1
EMX2	ENST00000442245.5 linkuse as main transcript	c.121T>G	p.Ser41Ala	missense_variant	1/2	2		ENSP00000474874.1	Q04743-2

Frequencies

GnomAD3 genomes

AF:

0.000184

AC:

AN:

151766

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000654

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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:

0.000479

GnomAD3 exomes

AF:

0.0000526

AC:

AN:

190058

Hom.:

AF XY:

0.0000193

AC XY:

AN XY:

103360

show subpopulations

Gnomad AFR exome

AF:

0.000879

Gnomad AMR exome

AF:

0.0000343

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:

0.0000273

AC:

AN:

1429094

Hom.:

Cov.:

AF XY:

0.0000212

AC XY:

AN XY:

708048

show subpopulations

Gnomad4 AFR exome

AF:

0.00111

Gnomad4 AMR exome

AF:

0.0000248

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:

0.0000338

GnomAD4 genome

AF:

0.000184

AC:

AN:

151880

Hom.:

Cov.:

AF XY:

0.000121

AC XY:

AN XY:

74252

show subpopulations

Gnomad4 AFR

AF:

0.000652

Gnomad4 AMR

AF:

0.00

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:

0.000474

Alfa

AF:

0.000155

Hom.:

Bravo

AF:

0.000234

ESP6500AA

AF:

0.000470

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.0000170

AC:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Inborn genetic diseases

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Oct 12, 2021

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.073

BayesDel_addAF

Benign

-0.28

BayesDel_noAF

Benign

-0.24

CADD

Uncertain

DANN

Benign

0.65

DEOGEN2

Benign

0.36

T;.

Eigen

Benign

-0.21

Eigen_PC

Benign

0.028

FATHMM_MKL

Uncertain

0.94

LIST_S2

Benign

0.69

T;T

M_CAP

Pathogenic

0.96

MetaRNN

Benign

0.11

T;T

MetaSVM

Benign

-0.29

MutationAssessor

Benign

1.2

L;L

PrimateAI

Pathogenic

0.81

PROVEAN

Benign

-1.3

N;.

REVEL

Benign

0.26

Sift

Benign

0.27

T;.

Sift4G

Benign

0.62

T;T

Polyphen

0.0

B;.

Vest4

0.20

MVP

0.82

ClinPred

0.024

GERP RS

5.8

Varity_R

0.23

gMVP

0.61

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