2-72917892-C-G

Variant names:

• chr2-72917892-C-G
• rs1231655247
• NM_004097.3:c.40C>G

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 0P and 5B. BP4 BS2

The NM_004097.3(EMX1):​c.40C>G​(p.Pro14Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000257 in 1,480,204 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. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 33)
  • Exomes 𝑓: 0.000028 (0 hom.)
• Consequence: EMX1 NM_004097.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.63
• Publications: 1 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: Likely_benign. The variant received -5 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.2954313).
• BS2: High AC in GnomAdExome4 at 37 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.40C>G	p.Pro14Ala	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.40C>G	p.Pro14Ala	missense	Exon 1 of 3	ENSP00000258106.6	Q04741-1
	EMX1	ENST00000967897.1		c.40C>G	p.Pro14Ala	missense	Exon 1 of 3	ENSP00000637956.1
	EMX1	ENST00000394111.6	TSL:3	c.377+832C>G		intron	N/A	ENSP00000482619.1	A0A087WZF2

Frequencies

GnomAD3 genomes AF: 0.00000659 AC: 1 AN: 151840 Hom.: 0 Cov.: 33

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: 0.0000147

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000124 AC: 1 AN: 80536 AF XY: 0.00

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: 0.0000351

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000279 AC: 37 AN: 1328364 Hom.: 0 Cov.: 31 AF XY: 0.0000229 AC XY: 15 AN XY: 654872

African (AFR) AF: 0.00 AC: 0 AN: 26916

American (AMR) AF: 0.00 AC: 0 AN: 28012

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 23532

East Asian (EAS) AF: 0.00 AC: 0 AN: 28532

South Asian (SAS) AF: 0.00 AC: 0 AN: 74112

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 32912

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3940

European-Non Finnish (NFE) AF: 0.0000351 AC: 37 AN: 1055174

Other (OTH) AF: 0.00 AC: 0 AN: 55234

GnomAD4 genome AF: 0.00000659 AC: 1 AN: 151840 Hom.: 0 Cov.: 33 AF XY: 0.0000135 AC XY: 1 AN XY: 74172

African (AFR) AF: 0.00 AC: 0 AN: 41414

American (AMR) AF: 0.00 AC: 0 AN: 15250

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5176

South Asian (SAS) AF: 0.00 AC: 0 AN: 4834

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10482

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

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 67904

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

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000756

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.046
BayesDel_addAF	Benign	-0.040	T
BayesDel_noAF	Benign	-0.30
CADD	Benign	23
DANN	Uncertain	0.99
Eigen	Benign	-0.074
Eigen_PC	Benign	-0.088
FATHMM_MKL	Benign	0.43	N
M_CAP	Pathogenic	0.93	D
MetaRNN	Benign	0.30	T
MetaSVM	Benign	-0.36	T
PhyloP100		1.6
PrimateAI	Pathogenic	0.87	D
PROVEAN	Benign	-0.97	N
REVEL	Benign	0.19
Sift	Benign	0.18	T
Sift4G	Benign	0.19	T
Vest4		0.24
MutPred		0.33		Loss of loop (P = 0.0022)
MVP		0.66
MPC		1.8
ClinPred		0.48	T
GERP RS		1.7
PromoterAI		0.017	Neutral
gMVP		0.16
Mutation Taster		=90/10	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: rs1231655247; hg19: chr2-73145021;