chr2-72924356-C-T

Variant names:

• chr2-72924356-C-T
• rs1304203842
• NM_004097.3:c.568C>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PP3_Moderate BS2

The NM_004097.3(EMX1):​c.568C>T​(p.Arg190Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000627 in 1,434,396 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000063 (0 hom.)
• Consequence: EMX1 NM_004097.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.876
• 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 -2 ACMG points.

• PP3: MetaRNN computational evidence supports a deleterious effect, 0.85
• BS2: High AC in GnomAdExome4 at 9 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.568C>T	p.Arg190Cys	missense	Exon 2 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.568C>T	p.Arg190Cys	missense	Exon 2 of 3	ENSP00000258106.6	Q04741-1
	EMX1	ENST00000967897.1		c.568C>T	p.Arg190Cys	missense	Exon 2 of 3	ENSP00000637956.1
	EMX1	ENST00000394111.6	TSL:3	c.425C>T	p.Thr142Met	missense	Exon 2 of 3	ENSP00000482619.1	A0A087WZF2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD2 exomes AF: 0.0000204 AC: 4 AN: 196214 AF XY: 0.0000185

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: 0.0000460

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000627 AC: 9 AN: 1434396 Hom.: 0 Cov.: 32 AF XY: 0.00000562 AC XY: 4 AN XY: 712090

African (AFR) AF: 0.00 AC: 0 AN: 33366

American (AMR) AF: 0.00 AC: 0 AN: 41224

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25616

East Asian (EAS) AF: 0.00 AC: 0 AN: 38932

South Asian (SAS) AF: 0.00 AC: 0 AN: 82818

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 42336

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5728

European-Non Finnish (NFE) AF: 0.00000815 AC: 9 AN: 1104706

Other (OTH) AF: 0.00 AC: 0 AN: 59670

GnomAD4 genome Cov.: 33

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	Uncertain	0.38
BayesDel_addAF	Pathogenic	0.35	D
BayesDel_noAF	Pathogenic	0.26
CADD	Pathogenic	34
DANN	Pathogenic	1.0
Eigen	Uncertain	0.35
Eigen_PC	Uncertain	0.36
FATHMM_MKL	Benign	0.70	D
LIST_S2	Pathogenic	0.98	D
M_CAP	Benign	0.082	D
MetaRNN	Pathogenic	0.85	D
MetaSVM	Uncertain	-0.27	T
PhyloP100		0.88
PrimateAI	Pathogenic	0.88	D
PROVEAN	Pathogenic	-6.9	D
REVEL	Pathogenic	0.77
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0010	D
Vest4		0.71
MVP		0.95
MPC		2.4
ClinPred		0.96	D
GERP RS		4.5
gMVP		0.81
Mutation Taster		=17/83	disease causing

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs1304203842; hg19: chr2-73151485; COSMIC: COSV50689195;