chr10-117543372-A-T

Variant names:

• chr10-117543372-A-T
• rs373030604
• NM_004098.4:c.105A>T

Variant summary

Our verdict is Benign. The variant received -17 ACMG points: 0P and 17B. BP4_Strong BP6_Very_Strong BP7 BS2

The NM_004098.4(EMX2):​c.105A>T​(p.Ala35Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000426 in 1,571,416 control chromosomes in the GnomAD database, including 5 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.00070 (1 hom., cov: 29)
  • Exomes 𝑓: 0.00040 (4 hom.)
• Consequence: EMX2 NM_004098.4 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: -0.178
• Publications: 1 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 -17 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.76).
• BP6: Variant 10-117543372-A-T is Benign according to our data. Variant chr10-117543372-A-T is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 193271.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.178 with no splicing effect.
• BS2: High AC in GnomAd4 at 106 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.105A>T	p.Ala35Ala	synonymous	Exon 1 of 3	NP_004089.1	Q04743-1
	EMX2	NM_001165924.2		c.105A>T	p.Ala35Ala	synonymous	Exon 1 of 2	NP_001159396.1	Q04743-2
	EMX2OS	NR_002791.2		n.574+934T>A		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EMX2	ENST00000553456.5	TSL:1 MANE Select	c.105A>T	p.Ala35Ala	synonymous	Exon 1 of 3	ENSP00000450962.3	Q04743-1
	EMX2OS	ENST00000551288.5	TSL:1	n.574+934T>A		intron	N/A
	EMX2	ENST00000442245.5	TSL:2	c.105A>T	p.Ala35Ala	synonymous	Exon 1 of 2	ENSP00000474874.1	Q04743-2

Frequencies

GnomAD3 genomes AF: 0.000692 AC: 105 AN: 151692 Hom.: 1 Cov.: 29

Gnomad AFR AF: 0.000509

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00446

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00136

Gnomad SAS AF: 0.000209

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000884

Gnomad OTH AF: 0.000959

GnomAD2 exomes AF: 0.00185 AC: 328 AN: 177430 AF XY: 0.00140

Gnomad AFR exome AF: 0.000635

Gnomad AMR exome AF: 0.0105

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00133

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000411

Gnomad OTH exome AF: 0.00211

GnomAD4 exome AF: 0.000397 AC: 564 AN: 1419614 Hom.: 4 Cov.: 32 AF XY: 0.000377 AC XY: 265 AN XY: 702478

African (AFR) AF: 0.000372 AC: 12 AN: 32254

American (AMR) AF: 0.0108 AC: 418 AN: 38708

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25358

East Asian (EAS) AF: 0.00163 AC: 60 AN: 36734

South Asian (SAS) AF: 0.000135 AC: 11 AN: 81340

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 49200

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5716

European-Non Finnish (NFE) AF: 0.0000339 AC: 37 AN: 1091472

Other (OTH) AF: 0.000442 AC: 26 AN: 58832

GnomAD4 genome AF: 0.000698 AC: 106 AN: 151802 Hom.: 1 Cov.: 29 AF XY: 0.000687 AC XY: 51 AN XY: 74198

African (AFR) AF: 0.000507 AC: 21 AN: 41398

American (AMR) AF: 0.00452 AC: 69 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3460

East Asian (EAS) AF: 0.00136 AC: 7 AN: 5142

South Asian (SAS) AF: 0.000209 AC: 1 AN: 4792

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10552

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 290

European-Non Finnish (NFE) AF: 0.0000884 AC: 6 AN: 67884

Other (OTH) AF: 0.000949 AC: 2 AN: 2108

Alfa AF: 0.000335 Hom.: 0

Bravo AF: 0.00110

Asia WGS AF: 0.00231 AC: 8 AN: 3474

ClinVar

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not provided (3)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.76
CADD	Benign	10
DANN	Benign	0.91
PhyloP100		-0.18
PromoterAI		0.022	Neutral
Mutation Taster		=98/2	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: rs373030604; hg19: chr10-119302883;