chr2-72918283-C-A

Variant names:

• chr2-72918283-C-A
• rs760283603
• NM_004097.3:c.431C>A

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BS2

The NM_004097.3(EMX1):​c.431C>A​(p.Pro144Gln) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000421 in 1,423,818 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000042 (0 hom.)
• Consequence: EMX1 NM_004097.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.56
• 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 -4 ACMG points.

• 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.431C>A	p.Pro144Gln	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.431C>A	p.Pro144Gln	missense	Exon 1 of 3	ENSP00000258106.6	Q04741-1
	EMX1	ENST00000967897.1		c.431C>A	p.Pro144Gln	missense	Exon 1 of 3	ENSP00000637956.1
	EMX1	ENST00000473732.1	TSL:3	c.65C>A	p.Pro22Gln	missense	Exon 1 of 3	ENSP00000446992.1	F8W1B5

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD2 exomes AF: 0.00000509 AC: 1 AN: 196620 AF XY: 0.00000901

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: 0.0000110

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000421 AC: 6 AN: 1423818 Hom.: 0 Cov.: 31 AF XY: 0.00000282 AC XY: 2 AN XY: 708632

African (AFR) AF: 0.00 AC: 0 AN: 30754

American (AMR) AF: 0.00 AC: 0 AN: 41606

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25430

East Asian (EAS) AF: 0.00 AC: 0 AN: 36574

South Asian (SAS) AF: 0.00 AC: 0 AN: 83516

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 37264

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5704

European-Non Finnish (NFE) AF: 0.00000544 AC: 6 AN: 1103750

Other (OTH) AF: 0.00 AC: 0 AN: 59220

GnomAD4 genome Cov.: 33

ExAC AF: 0.00000860 AC: 1

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	0.13
BayesDel_addAF	Pathogenic	0.18	D
BayesDel_noAF	Uncertain	0.010
CADD	Pathogenic	29
DANN	Uncertain	0.99
Eigen	Uncertain	0.62
Eigen_PC	Uncertain	0.56
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Benign	0.74	T
M_CAP	Pathogenic	0.94	D
MetaRNN	Uncertain	0.71	D
MetaSVM	Uncertain	0.74	D
PhyloP100		7.6
PrimateAI	Pathogenic	0.82	D
PROVEAN	Benign	-1.4	N
REVEL	Uncertain	0.55
Sift	Benign	0.053	T
Sift4G	Benign	0.098	T
Vest4		0.46
MVP		0.77
MPC		2.0
ClinPred		0.95	D
GERP RS		3.7
PromoterAI		-0.015	Neutral
gMVP		0.73
Mutation Taster		=41/59	disease causing

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: rs760283603; hg19: chr2-73145412; COSMIC: COSV99252324;