2-72917892-C-T

Variant names:

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

Variant summary

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

The NM_004097.3(EMX1):​c.40C>T​(p.Pro14Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000151 in 1,328,364 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict 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. P14A) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000015 (0 hom.)
• Consequence: EMX1 NM_004097.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.63
• 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=0.31803784).

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>T	p.Pro14Ser	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>T	p.Pro14Ser	missense	Exon 1 of 3	ENSP00000258106.6	Q04741-1
	EMX1	ENST00000967897.1		c.40C>T	p.Pro14Ser	missense	Exon 1 of 3	ENSP00000637956.1
	EMX1	ENST00000394111.6	TSL:3	c.377+832C>T		intron	N/A	ENSP00000482619.1	A0A087WZF2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000151 AC: 2 AN: 1328364 Hom.: 0 Cov.: 31 AF XY: 0.00000305 AC XY: 2 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: 0.00000190 AC: 2 AN: 1055174

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

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.095
BayesDel_addAF	Benign	-0.032	T
BayesDel_noAF	Benign	-0.28
CADD	Uncertain	25
DANN	Uncertain	1.0
Eigen	Benign	-0.074
Eigen_PC	Benign	-0.088
FATHMM_MKL	Benign	0.41	N
M_CAP	Pathogenic	0.94	D
MetaRNN	Benign	0.32	T
MetaSVM	Benign	-0.36	T
PhyloP100		1.6
PrimateAI	Pathogenic	0.87	D
PROVEAN	Benign	-1.1	N
REVEL	Benign	0.20
Sift	Uncertain	0.0080	D
Sift4G	Benign	0.12	T
Vest4		0.22
MutPred		0.30		Loss of loop (P = 0.0073)
MVP		0.68
MPC		1.9
ClinPred		0.77	D
GERP RS		1.7
PromoterAI		0.041	Neutral
gMVP		0.28
Mutation Taster		=92/8	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;