2-72918283-C-A

Variant summary

Our verdict is Likely benign. Variant got -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

Scores

4
7
5

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.56
Variant links:
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

BS2
High AC in GnomAdExome4 at 6 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
EMX1NM_004097.3 linkc.431C>A p.Pro144Gln missense_variant Exon 1 of 3 ENST00000258106.11 NP_004088.2 Q04741-1
EMX1XM_011532697.4 linkc.7+1219C>A intron_variant Intron 1 of 2 XP_011530999.1 Q04741-2

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
EMX1ENST00000258106.11 linkc.431C>A p.Pro144Gln missense_variant Exon 1 of 3 1 NM_004097.3 ENSP00000258106.6 Q04741-1
EMX1ENST00000473732.1 linkc.65C>A p.Pro22Gln missense_variant Exon 1 of 3 3 ENSP00000446992.1 F8W1B5
EMX1ENST00000394111.6 linkc.377+1223C>A intron_variant Intron 1 of 2 3 ENSP00000482619.1 A0A087WZF2

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD3 exomes
AF:
0.00000509
AC:
1
AN:
196620
Hom.:
0
AF XY:
0.00000901
AC XY:
1
AN XY:
110936
show subpopulations
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 SAS 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
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000544
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
33
ExAC
AF:
0.00000860
AC:
1

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Jul 30, 2024
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.431C>A (p.P144Q) alteration is located in exon 1 (coding exon 1) of the EMX1 gene. This alteration results from a C to A substitution at nucleotide position 431, causing the proline (P) at amino acid position 144 to be replaced by a glutamine (Q). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
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;D
MetaSVM
Uncertain
0.74
D
PrimateAI
Pathogenic
0.82
D
PROVEAN
Benign
-1.4
N;N
REVEL
Uncertain
0.55
Sift
Benign
0.053
T;D
Sift4G
Benign
0.098
T;D
Vest4
0.46
MVP
0.77
MPC
2.0
ClinPred
0.95
D
GERP RS
3.7
gMVP
0.73

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

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