NM_004097.3:c.394C>G

Variant names:

• chr2-72918246-C-G
• rs755432277
• NM_004097.3:c.394C>G

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_004097.3(EMX1):​c.394C>G​(p.Pro132Ala) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts 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. P132S) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 33)
• Consequence: EMX1 NM_004097.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.90
• Publications: 0 publications found

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]

ACMG classification

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=0.3854457).

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.394C>G	p.Pro132Ala	missense	Exon 1 of 3	NP_004088.2	Q04741-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EMX1	ENST00000258106.11	TSL:1 MANE Select	c.394C>G	p.Pro132Ala	missense	Exon 1 of 3	ENSP00000258106.6	Q04741-1
	EMX1	ENST00000967897.1		c.394C>G	p.Pro132Ala	missense	Exon 1 of 3	ENSP00000637956.1
	EMX1	ENST00000473732.1	TSL:3	c.28C>G	p.Pro10Ala	missense	Exon 1 of 3	ENSP00000446992.1	F8W1B5

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Uncertain	0.10	D
BayesDel_noAF	Benign	-0.090
CADD	Uncertain	25
DANN	Uncertain	0.99
Eigen	Benign	-0.033
Eigen_PC	Benign	0.078
FATHMM_MKL	Benign	0.69	D
LIST_S2	Benign	0.60	T
M_CAP	Pathogenic	0.97	D
MetaRNN	Benign	0.39	T
MetaSVM	Uncertain	0.31	D
PhyloP100		4.9
PrimateAI	Pathogenic	0.88	D
PROVEAN	Benign	-2.3	N
REVEL	Uncertain	0.37
Sift	Uncertain	0.024	D
Sift4G	Benign	0.26	T
Vest4		0.28
MVP		0.74
MPC		1.1
ClinPred		0.96	D
GERP RS		3.9
PromoterAI		-0.13	Neutral
gMVP		0.67
Mutation Taster		=88/12	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: rs755432277; hg19: chr2-73145375;