10-117543440-C-T

Variant names:

• chr10-117543440-C-T
• rs549784838
• NM_004098.4:c.173C>T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_004098.4(EMX2):​c.173C>T​(p.Ala58Val) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 29)
• Consequence: EMX2 NM_004098.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.07

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]

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

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.3840208).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EMX2	NM_004098.4	c.173C>T	p.Ala58Val	missense_variant	Exon 1 of 3	ENST00000553456.5	NP_004089.1
EMX2	NM_001165924.2	c.173C>T	p.Ala58Val	missense_variant	Exon 1 of 2		NP_001159396.1
EMX2OS	NR_002791.2	n.574+866G>A		intron_variant	Intron 2 of 3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EMX2	ENST00000553456.5	c.173C>T	p.Ala58Val	missense_variant	Exon 1 of 3	1	NM_004098.4	ENSP00000450962.3
EMX2OS	ENST00000551288.5	n.574+866G>A		intron_variant	Intron 2 of 3	1
EMX2	ENST00000442245.5	c.173C>T	p.Ala58Val	missense_variant	Exon 1 of 2	2		ENSP00000474874.1
EMX2	ENST00000616794.1	c.-128C>T		upstream_gene_variant		2		ENSP00000480271.1

Frequencies

GnomAD3 genomes Cov.: 29

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 29

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Uncertain	0.070	D
BayesDel_noAF	Benign	-0.14
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.44	T;.
Eigen	Benign	-0.23
Eigen_PC	Benign	-0.013
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Benign	0.68	T;T
M_CAP	Pathogenic	0.89	D
MetaRNN	Benign	0.38	T;T
MetaSVM	Uncertain	-0.093	T
MutationAssessor	Benign	0.0	N;N
PrimateAI	Uncertain	0.68	T
PROVEAN	Benign	-1.5	N;.
REVEL	Benign	0.28
Sift	Benign	0.036	D;.
Sift4G	Benign	0.14	T;D
Polyphen		0.0	B;.
Vest4		0.28
MutPred		0.37		Loss of helix (P = 0.0093);Loss of helix (P = 0.0093);
MVP		0.85
ClinPred		0.76	D
GERP RS		4.9
Varity_R		0.12
gMVP		0.60

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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

Other links and lift over

dbSNP: rs549784838; hg19: chr10-119302951;