10-117543289-C-A

Variant names:

• chr10-117543289-C-A
• NM_004098.4:c.22C>A

Variant summary

Our verdict is Likely benign. Variant got -3 ACMG points: 1P and 4B. PP3 BS2

The NM_004098.4(EMX2):​c.22C>A​(p.Arg8Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00001 in 1,397,112 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 29)
  • Exomes 𝑓: 0.000010 (0 hom.)
• Consequence: EMX2 NM_004098.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.71

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 Likely_benign. Variant got -3 ACMG points.

• PP3: MetaRNN computational evidence supports a deleterious effect, 0.796
• BS2: High AC in GnomAdExome4 at 14 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EMX2	NM_004098.4	c.22C>A	p.Arg8Ser	missense_variant	Exon 1 of 3	ENST00000553456.5	NP_004089.1
EMX2	NM_001165924.2	c.22C>A	p.Arg8Ser	missense_variant	Exon 1 of 2		NP_001159396.1
EMX2OS	NR_002791.2	n.574+1017G>T		intron_variant	Intron 2 of 3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EMX2	ENST00000553456.5	c.22C>A	p.Arg8Ser	missense_variant	Exon 1 of 3	1	NM_004098.4	ENSP00000450962.3
EMX2OS	ENST00000551288.5	n.574+1017G>T		intron_variant	Intron 2 of 3	1
EMX2	ENST00000442245.5	c.22C>A	p.Arg8Ser	missense_variant	Exon 1 of 2	2		ENSP00000474874.1

Frequencies

GnomAD3 genomes Cov.: 29

GnomAD4 exome AF: 0.0000100 AC: 14 AN: 1397112 Hom.: 0 Cov.: 32 AF XY: 0.0000102 AC XY: 7 AN XY: 689092

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

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: 0.0000121

Gnomad4 OTH exome AF: 0.0000173

GnomAD4 genome Cov.: 29

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.94
BayesDel_addAF	Pathogenic	0.44	D
BayesDel_noAF	Pathogenic	0.39
CADD	Pathogenic	28
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.43	T;.
Eigen	Uncertain	0.41
Eigen_PC	Uncertain	0.47
FATHMM_MKL	Uncertain	0.92	D
LIST_S2	Pathogenic	0.98	D;D
M_CAP	Pathogenic	0.85	D
MetaRNN	Pathogenic	0.80	D;D
MetaSVM	Uncertain	0.59	D
MutationAssessor	Uncertain	2.2	M;M
PrimateAI	Pathogenic	0.89	D
PROVEAN	Uncertain	-4.0	D;.
REVEL	Pathogenic	0.69
Sift	Uncertain	0.0020	D;.
Sift4G	Benign	0.27	T;D
Polyphen		0.97	D;.
Vest4		0.78
MutPred		0.42		Gain of ubiquitination at K7 (P = 0.0438);Gain of ubiquitination at K7 (P = 0.0438);
MVP		0.99
ClinPred		0.98	D
GERP RS		5.5
Varity_R		0.36
gMVP		0.81

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.

Other links and lift over

hg19: chr10-119302800;