rs371549541

Variant names:

• chr10-117543280-G-C
• rs371549541
• NM_004098.4:c.13G>C

Your query was ambiguous. Multiple possible variants found:

• chr10-117543280-G-C
• chr10-117543280-G-A

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 0P and 5B. BP4 BS2

The NM_004098.4(EMX2):​c.13G>C​(p.Ala5Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000775 in 1,548,030 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A5G) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.000013 (0 hom., cov: 29)
  • Exomes 𝑓: 0.0000072 (0 hom.)
• Consequence: EMX2 NM_004098.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.93
• Publications: 0 publications found

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

Our verdict: Likely_benign. The variant received -5 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.4098162).
• BS2: High AC in GnomAdExome4 at 10 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EMX2	NM_004098.4	MANE Select	c.13G>C	p.Ala5Pro	missense	Exon 1 of 3	NP_004089.1	Q04743-1
	EMX2	NM_001165924.2		c.13G>C	p.Ala5Pro	missense	Exon 1 of 2	NP_001159396.1	Q04743-2
	EMX2OS	NR_002791.2		n.574+1026C>G		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EMX2	ENST00000553456.5	TSL:1 MANE Select	c.13G>C	p.Ala5Pro	missense	Exon 1 of 3	ENSP00000450962.3	Q04743-1
	EMX2OS	ENST00000551288.5	TSL:1	n.574+1026C>G		intron	N/A
	EMX2	ENST00000442245.5	TSL:2	c.13G>C	p.Ala5Pro	missense	Exon 1 of 2	ENSP00000474874.1	Q04743-2

Frequencies

GnomAD3 genomes AF: 0.0000132 AC: 2 AN: 151776 Hom.: 0 Cov.: 29

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000392

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.00000683 AC: 1 AN: 146480 AF XY: 0.0000127

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.000234

GnomAD4 exome AF: 0.00000716 AC: 10 AN: 1396254 Hom.: 0 Cov.: 32 AF XY: 0.00000726 AC XY: 5 AN XY: 688584

African (AFR) AF: 0.00 AC: 0 AN: 31406

American (AMR) AF: 0.00 AC: 0 AN: 35640

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25102

East Asian (EAS) AF: 0.0000843 AC: 3 AN: 35608

South Asian (SAS) AF: 0.00 AC: 0 AN: 79080

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 48038

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5444

European-Non Finnish (NFE) AF: 9.28e-7 AC: 1 AN: 1078080

Other (OTH) AF: 0.000104 AC: 6 AN: 57856

GnomAD4 genome AF: 0.0000132 AC: 2 AN: 151776 Hom.: 0 Cov.: 29 AF XY: 0.00 AC XY: 0 AN XY: 74094

African (AFR) AF: 0.00 AC: 0 AN: 41326

American (AMR) AF: 0.00 AC: 0 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.000392 AC: 2 AN: 5108

South Asian (SAS) AF: 0.00 AC: 0 AN: 4806

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10580

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 314

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67912

Other (OTH) AF: 0.00 AC: 0 AN: 2088

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000264

Asia WGS AF: 0.000578 AC: 2 AN: 3476

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	Inborn genetic diseases (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Uncertain	0.13	D
BayesDel_noAF	Uncertain	-0.060
CADD	Uncertain	25
DANN	Benign	0.91
DEOGEN2	Benign	0.30	T
Eigen	Benign	0.15
Eigen_PC	Uncertain	0.29
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Uncertain	0.91	D
M_CAP	Pathogenic	0.90	D
MetaRNN	Benign	0.41	T
MetaSVM	Uncertain	0.19	D
MutationAssessor	Benign	0.69	N
PhyloP100		2.9
PrimateAI	Pathogenic	0.82	D
PROVEAN	Benign	-2.1	N
REVEL	Uncertain	0.39
Sift	Benign	0.16	T
Sift4G	Benign	0.26	T
Polyphen		0.0010	B
Vest4		0.30
MutPred		0.31		Gain of glycosylation at A5 (P = 0.002)
MVP		0.86
ClinPred		0.16	T
GERP RS		5.5
PromoterAI		0.046	Neutral
Varity_R		0.15
gMVP		0.76
Mutation Taster		=70/30	polymorphism

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

Other links and lift over

dbSNP: rs371549541; hg19: chr10-119302791;