Variant chr10-117543368-C-T details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_004098.4(EMX2):c.101C>T(p.Ala34Val) variant causes a missense change. The variant allele was found at a frequency of 0.000000706 in 1,417,306 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 29)

Exomes 𝑓: 7.1e-7 ( 0 hom. )

Consequence

EMX2
NM_004098.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.91

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:

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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
EMX2	NM_004098.4 linkuse as main transcript	c.101C>T	p.Ala34Val	missense_variant	1/3	ENST00000553456.5	NP_004089.1
EMX2OS	NR_002791.2 linkuse as main transcript	n.574+938G>A		intron_variant, non_coding_transcript_variant
EMX2	NM_001165924.2 linkuse as main transcript	c.101C>T	p.Ala34Val	missense_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.101C>T	p.Ala34Val	missense_variant	1/3	1	NM_004098.4	ENSP00000450962	P1	Q04743-1
EMX2OS	ENST00000551288.5 linkuse as main transcript	n.574+938G>A		intron_variant, non_coding_transcript_variant		1
EMX2	ENST00000442245.5 linkuse as main transcript	c.101C>T	p.Ala34Val	missense_variant	1/2	2		ENSP00000474874		Q04743-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

7.06e-7

AC:

AN:

1417306

Hom.:

Cov.:

AF XY:

0.00000143

AC XY:

AN XY:

701036

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000261

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:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Inborn genetic diseases

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 21, 2023

The c.101C>T (p.A34V) alteration is located in exon 1 (coding exon 1) of the EMX2 gene. This alteration results from a C to T substitution at nucleotide position 101, causing the alanine (A) at amino acid position 34 to be replaced by a valine (V). 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

0.29

BayesDel_addAF

Pathogenic

0.25

BayesDel_noAF

Uncertain

0.12

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.42

T;.

Eigen

Benign

0.18

Eigen_PC

Uncertain

0.29

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.96

D;D

M_CAP

Pathogenic

0.96

MetaRNN

Uncertain

0.55

D;D

MetaSVM

Uncertain

0.0049

MutationAssessor

Benign

1.9

L;L

MutationTaster

Benign

1.0

D;D

PrimateAI

Uncertain

0.79

PROVEAN

Benign

-1.3

N;.

REVEL

Uncertain

0.52

Sift

Uncertain

0.024

D;.

Sift4G

Uncertain

0.033

D;D

Polyphen

0.88

P;.

Vest4

0.40

MutPred

0.35

Loss of disorder (P = 0.0724);Loss of disorder (P = 0.0724);

MVP

0.94

ClinPred

0.94

GERP RS

4.8

Varity_R

0.21

gMVP

0.71

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

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