Genetic Variant EMX1:p.Ala70Val (chr2-72918061-C-T) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2BP4

The NM_004097.3(EMX1):c.209C>T(p.Ala70Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000212 in 1,415,088 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A70E) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0000016 ( 0 hom. )

Consequence

EMX1
NM_004097.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 3.39

Publications

0 publications found

Variant links:

Genes affected

EMX1 (HGNC:3340): (empty spiracles homeobox 1) Enables sequence-specific double-stranded DNA binding activity. Predicted to be involved in brain development; neuron differentiation; and regulation of transcription by RNA polymerase II. Predicted to act upstream of or within several processes, including nervous system development; neuroepithelial cell differentiation; and regulation of oligodendrocyte progenitor proliferation. Located in chromosome and nucleolus. [provided by Alliance of Genome Resources, Apr 2022]

EMX1 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.4203986).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004097.3. 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
	EMX1	NM_004097.3	MANE Select	c.209C>T	p.Ala70Val	missense	Exon 1 of 3	NP_004088.2	Q04741-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
EMX1	ENST00000258106.11	TSL:1 MANE Select	c.209C>T	p.Ala70Val	missense	Exon 1 of 3	ENSP00000258106.6	Q04741-1
EMX1	ENST00000967897.1		c.209C>T	p.Ala70Val	missense	Exon 1 of 3	ENSP00000637956.1
EMX1	ENST00000394111.6	TSL:3	c.377+1001C>T		intron	N/A	ENSP00000482619.1	A0A087WZF2

Frequencies

GnomAD3 genomes

AF:

0.00000663

AC:

AN:

150914

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

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:

0.0000148

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.00000158

AC:

AN:

1264174

Hom.:

Cov.:

AF XY:

0.00000161

AC XY:

AN XY:

619266

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

25190

American (AMR)

AF:

0.00

AC:

AN:

16268

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

19774

East Asian (EAS)

AF:

0.00

AC:

AN:

27772

South Asian (SAS)

AF:

0.00

AC:

AN:

61504

European-Finnish (FIN)

AF:

0.00

AC:

AN:

30790

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3740

European-Non Finnish (NFE)

AF:

0.00000195

AC:

AN:

1026738

Other (OTH)

AF:

0.00

AC:

AN:

52398

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.550

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.00000663

AC:

AN:

150914

Hom.:

Cov.:

AF XY:

0.0000136

AC XY:

AN XY:

73748

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41056

American (AMR)

AF:

0.00

AC:

AN:

15212

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3466

East Asian (EAS)

AF:

0.00

AC:

AN:

5030

South Asian (SAS)

AF:

0.00

AC:

AN:

4764

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10496

Middle Eastern (MID)

AF:

0.00

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.0000148

AC:

AN:

67628

Other (OTH)

AF:

0.00

AC:

AN:

2070

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.14

BayesDel_addAF

Benign

-0.029

BayesDel_noAF

Benign

-0.28

CADD

Benign

(source)

DANN

Uncertain

1.0

Eigen

Benign

-0.16

Eigen_PC

Benign

-0.058

FATHMM_MKL

Benign

0.75

M_CAP

Pathogenic

0.99

MetaRNN

Benign

0.42

MetaSVM

Uncertain

-0.099

PhyloP100

3.4

PrimateAI

Pathogenic

0.86

PROVEAN

Benign

-0.54

REVEL

Benign

0.25

Sift

Benign

0.27

Sift4G

Benign

0.44

Vest4

0.25

MVP

0.75

MPC

1.1

ClinPred

0.35

GERP RS

2.7

PromoterAI

-0.013

Neutral

(source)

gMVP

0.27

Mutation Taster

=92/8

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over