chr2-72917967-G-A

Variant names:

• chr2-72917967-G-A
• rs1442868584
• NM_004097.3:c.115G>A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_004097.3(EMX1):​c.115G>A​(p.Ala39Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000015 in 1,335,500 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: not found (cov: 33)
  • Exomes 𝑓: 0.0000015 (0 hom.)
• Consequence: EMX1 NM_004097.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.05
• 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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.16902024).

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.115G>A	p.Ala39Thr	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.115G>A	p.Ala39Thr	missense	Exon 1 of 3	ENSP00000258106.6	Q04741-1
	EMX1	ENST00000967897.1		c.115G>A	p.Ala39Thr	missense	Exon 1 of 3	ENSP00000637956.1
	EMX1	ENST00000394111.6	TSL:3	c.377+907G>A		intron	N/A	ENSP00000482619.1	A0A087WZF2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000150 AC: 2 AN: 1335500 Hom.: 0 Cov.: 31 AF XY: 0.00000304 AC XY: 2 AN XY: 658388

African (AFR) AF: 0.00 AC: 0 AN: 27062

American (AMR) AF: 0.00 AC: 0 AN: 29372

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 23700

East Asian (EAS) AF: 0.00 AC: 0 AN: 29284

South Asian (SAS) AF: 0.00 AC: 0 AN: 74794

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 33052

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4034

European-Non Finnish (NFE) AF: 0.00000189 AC: 2 AN: 1058554

Other (OTH) AF: 0.00 AC: 0 AN: 55648

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

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	0.12
BayesDel_addAF	Benign	-0.15	T
BayesDel_noAF	Benign	-0.45
CADD	Benign	22
DANN	Uncertain	0.99
Eigen	Benign	-0.98
Eigen_PC	Benign	-0.82
FATHMM_MKL	Benign	0.20	N
M_CAP	Pathogenic	0.98	D
MetaRNN	Benign	0.17	T
MetaSVM	Benign	-0.67	T
PhyloP100		1.0
PrimateAI	Pathogenic	0.89	D
PROVEAN	Benign	0.53	N
REVEL	Benign	0.21
Sift	Benign	0.94	T
Sift4G	Benign	0.30	T
Vest4		0.052
MVP		0.53
MPC		1.8
ClinPred		0.53	D
GERP RS		0.62
PromoterAI		0.0017	Neutral
gMVP		0.16
Mutation Taster		=96/4	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: rs1442868584; hg19: chr2-73145096;