Genetic Variant EMX1:p.Pro8Ser (chr2-72917874-C-T) – ACMG Classification: Likely_benign (-5 pts)

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 0P and 5B. BP4BS2

The NM_004097.3(EMX1):c.22C>T(p.Pro8Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000542 in 1,476,442 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0000045 ( 0 hom. )

Consequence

EMX1
NM_004097.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.734

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: Likely_benign. The variant received -5 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.2793261).

BS2

High AC in GnomAdExome4 at 6 AD gene.

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.22C>T	p.Pro8Ser	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.22C>T	p.Pro8Ser	missense	Exon 1 of 3	ENSP00000258106.6	Q04741-1
EMX1	ENST00000967897.1		c.22C>T	p.Pro8Ser	missense	Exon 1 of 3	ENSP00000637956.1
EMX1	ENST00000394111.6	TSL:3	c.377+814C>T		intron	N/A	ENSP00000482619.1	A0A087WZF2

Frequencies

GnomAD3 genomes

AF:

0.0000132

AC:

AN:

151804

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:

0.0000954

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000255

AC:

AN:

78460

AF XY:

0.0000446

show subpopulations

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:

0.000211

Gnomad NFE exome

AF:

0.0000361

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000453

AC:

AN:

1324638

Hom.:

Cov.:

AF XY:

0.00000459

AC XY:

AN XY:

652974

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

26820

American (AMR)

AF:

0.00

AC:

AN:

27484

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

23328

East Asian (EAS)

AF:

0.00

AC:

AN:

28352

South Asian (SAS)

AF:

0.00

AC:

AN:

73584

European-Finnish (FIN)

AF:

0.000152

AC:

AN:

32862

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3922

European-Non Finnish (NFE)

AF:

9.49e-7

AC:

AN:

1053288

Other (OTH)

AF:

0.00

AC:

AN:

54998

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.517

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0000132

AC:

AN:

151804

Hom.:

Cov.:

AF XY:

0.0000270

AC XY:

AN XY:

74160

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41402

American (AMR)

AF:

0.00

AC:

AN:

15246

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3468

East Asian (EAS)

AF:

0.00

AC:

AN:

5164

South Asian (SAS)

AF:

0.00

AC:

AN:

4836

European-Finnish (FIN)

AF:

0.0000954

AC:

AN:

10486

Middle Eastern (MID)

AF:

0.00

AC:

AN:

314

European-Non Finnish (NFE)

AF:

0.0000147

AC:

AN:

67886

Other (OTH)

AF:

0.00

AC:

AN:

2090

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

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

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.099

BayesDel_addAF

Benign

-0.023

BayesDel_noAF

Benign

-0.27

CADD

Uncertain

(source)

DANN

Uncertain

1.0

Eigen

Benign

-0.0082

Eigen_PC

Benign

-0.014

FATHMM_MKL

Benign

0.22

M_CAP

Pathogenic

0.98

MetaRNN

Benign

0.28

MetaSVM

Uncertain

0.11

PhyloP100

0.73

PrimateAI

Pathogenic

0.86

PROVEAN

Benign

-0.81

REVEL

Benign

0.11

Sift

Pathogenic

0.0

Sift4G

Benign

0.49

Vest4

0.19

MutPred

0.31

Gain of phosphorylation at P8 (P = 0.0385)

MVP

0.64

MPC

1.9

ClinPred

0.76

GERP RS

2.4

PromoterAI

-0.031

Neutral

(source)

gMVP

0.28

Mutation Taster

=97/3

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over