chr3-36992771-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_014805.4(EPM2AIP1):​c.307G>A​(p.Gly103Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000274 in 1,461,406 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: 0.0000027 ( 0 hom. )

Consequence

EPM2AIP1
NM_014805.4 missense

Scores

7
12

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.78
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 made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

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

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
EPM2AIP1NM_014805.4 linkuse as main transcriptc.307G>A p.Gly103Arg missense_variant 1/1 ENST00000322716.8

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
EPM2AIP1ENST00000322716.8 linkuse as main transcriptc.307G>A p.Gly103Arg missense_variant 1/1 NM_014805.4 P1
EPM2AIP1ENST00000623924.1 linkuse as main transcriptc.63+107G>A intron_variant 5

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
AF:
0.00000274
AC:
4
AN:
1461406
Hom.:
0
Cov.:
34
AF XY:
0.00000413
AC XY:
3
AN XY:
727020
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:
0.00000360
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
33

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingAmbry GeneticsJul 17, 2023The c.307G>A (p.G103R) alteration is located in exon 1 (coding exon 1) of the EPM2AIP1 gene. This alteration results from a G to A substitution at nucleotide position 307, causing the glycine (G) at amino acid position 103 to be replaced by an arginine (R). 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
AlphaMissense
Uncertain
0.55
BayesDel_addAF
Benign
-0.079
T
BayesDel_noAF
Benign
-0.35
CADD
Pathogenic
26
DANN
Uncertain
0.99
DEOGEN2
Benign
0.0029
T
Eigen
Benign
0.15
Eigen_PC
Uncertain
0.26
FATHMM_MKL
Uncertain
0.77
D
LIST_S2
Benign
0.73
T
M_CAP
Benign
0.0060
T
MetaRNN
Uncertain
0.54
D
MetaSVM
Benign
-1.1
T
MutationAssessor
Benign
1.6
L
MutationTaster
Benign
0.70
N
PrimateAI
Uncertain
0.59
T
PROVEAN
Benign
1.5
N
REVEL
Benign
0.14
Sift
Benign
0.65
T
Sift4G
Uncertain
0.028
D
Polyphen
0.63
P
Vest4
0.58
MutPred
0.74
Gain of helix (P = 0.0128);
MVP
0.45
MPC
1.4
ClinPred
0.94
D
GERP RS
4.4
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.1
Varity_R
0.12
gMVP
0.64

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr3-37034262; API