GeneBe

NM_014805.4:c.1177G>T

Variant names:

Variant summary

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

The NM_014805.4(EPM2AIP1):​c.1177G>T​(p.Glu393*) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,678 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 33)
Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

EPM2AIP1
NM_014805.4 stop_gained

Scores

2
3
2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.23

Publications

0 publications found
Variant links:
Genes affected
EPM2AIP1 (HGNC:19735): (EPM2A interacting protein 1) The EPM2A gene, which encodes laforin, is mutated in an autosomal recessive form of adolescent progressive myoclonus epilepsy. The protein encoded by this gene binds to laforin, but its function is not known. This gene is intronless. [provided by RefSeq, Oct 2008]

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
EPM2AIP1NM_014805.4 linkc.1177G>T p.Glu393* stop_gained Exon 1 of 1 ENST00000322716.8 NP_055620.1 Q7L775

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
EPM2AIP1ENST00000322716.8 linkc.1177G>T p.Glu393* stop_gained Exon 1 of 1 6 NM_014805.4 ENSP00000406027.1 Q7L775
EPM2AIP1ENST00000624586.1 linkc.367G>T p.Glu123* stop_gained Exon 1 of 2 5 ENSP00000485091.1 A0A096LNL1
EPM2AIP1ENST00000623924.1 linkc.62+977G>T intron_variant Intron 1 of 2 5 ENSP00000485489.1 A0A096LPB0

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
AF:
6.84e-7
AC:
1
AN:
1461678
Hom.:
0
Cov.:
33
AF XY:
0.00
AC XY:
0
AN XY:
727118
show subpopulations
African (AFR)
AF:
0.00
AC:
0
AN:
33480
American (AMR)
AF:
0.00
AC:
0
AN:
44724
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
26134
East Asian (EAS)
AF:
0.00
AC:
0
AN:
39696
South Asian (SAS)
AF:
0.00
AC:
0
AN:
86258
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
53384
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
5768
European-Non Finnish (NFE)
AF:
8.99e-7
AC:
1
AN:
1111860
Other (OTH)
AF:
0.00
AC:
0
AN:
60374
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.425
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Exome Het
Variant carriers
0
2
4
6
8
10
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
GnomAD4 genome
Cov.:
33
Alfa
AF:
0.00
Hom.:
0
Bravo
AF:
0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Pathogenic
0.57
D
BayesDel_noAF
Pathogenic
0.59
CADD
Pathogenic
35
DANN
Uncertain
1.0
Eigen
Uncertain
0.63
Eigen_PC
Uncertain
0.40
FATHMM_MKL
Benign
0.54
D
PhyloP100
2.2
Vest4
0.17
GERP RS
4.6
PromoterAI
0.018
Neutral
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.1
Mutation Taster
=29/171
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

Publications

Other links and lift over

dbSNP: rs1395557819; hg19: chr3-37033392; COSMIC: COSV51621264; COSMIC: COSV51621264; API