rs755940979

Variant names:

• chr10-117543348-C-G
• rs755940979
• NM_004098.4:c.81C>G

Your query was ambiguous. Multiple possible variants found:

• chr10-117543348-C-G
• chr10-117543348-C-T

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP4_Strong BP7 BS2

The NM_004098.4(EMX2):​c.81C>G​(p.Ser27Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000135 in 1,560,780 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 (★).

• Frequency:
  • Genomes: 𝑓 0.000026 (0 hom., cov: 29)
  • Exomes 𝑓: 0.000012 (0 hom.)
• Consequence: EMX2 NM_004098.4 synonymous
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.0650
• 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: Benign. The variant received -9 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.66).
• BP7: Synonymous conserved (PhyloP=-0.065 with no splicing effect.
• BS2: High AC in GnomAdExome4 at 17 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.81C>G	p.Ser27Ser	synonymous	Exon 1 of 3	NP_004089.1	Q04743-1
	EMX2	NM_001165924.2		c.81C>G	p.Ser27Ser	synonymous	Exon 1 of 2	NP_001159396.1	Q04743-2
	EMX2OS	NR_002791.2		n.574+958G>C		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EMX2	ENST00000553456.5	TSL:1 MANE Select	c.81C>G	p.Ser27Ser	synonymous	Exon 1 of 3	ENSP00000450962.3	Q04743-1
	EMX2OS	ENST00000551288.5	TSL:1	n.574+958G>C		intron	N/A
	EMX2	ENST00000442245.5	TSL:2	c.81C>G	p.Ser27Ser	synonymous	Exon 1 of 2	ENSP00000474874.1	Q04743-2

Frequencies

GnomAD3 genomes AF: 0.0000263 AC: 4 AN: 151998 Hom.: 0 Cov.: 29

Gnomad AFR AF: 0.0000483

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: 0.0000294

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.00000611 AC: 1 AN: 163776 AF XY: 0.0000114

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: 0.0000154

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000121 AC: 17 AN: 1408782 Hom.: 0 Cov.: 32 AF XY: 0.0000115 AC XY: 8 AN XY: 695972

African (AFR) AF: 0.0000313 AC: 1 AN: 31980

American (AMR) AF: 0.00 AC: 0 AN: 37040

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25252

East Asian (EAS) AF: 0.00 AC: 0 AN: 36244

South Asian (SAS) AF: 0.0000125 AC: 1 AN: 80210

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 48748

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5712

European-Non Finnish (NFE) AF: 0.0000129 AC: 14 AN: 1085204

Other (OTH) AF: 0.0000171 AC: 1 AN: 58392

GnomAD4 genome AF: 0.0000263 AC: 4 AN: 151998 Hom.: 0 Cov.: 29 AF XY: 0.0000269 AC XY: 2 AN XY: 74226

African (AFR) AF: 0.0000483 AC: 2 AN: 41388

American (AMR) AF: 0.00 AC: 0 AN: 15270

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 5164

South Asian (SAS) AF: 0.00 AC: 0 AN: 4816

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10598

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

European-Non Finnish (NFE) AF: 0.0000294 AC: 2 AN: 67978

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

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000264

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.66
CADD	Benign	4.1
DANN	Benign	0.53
PhyloP100		-0.065
PromoterAI		0.0027	Neutral

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: rs755940979; hg19: chr10-119302859;