rs137852781
Positions:
Variant summary
Our verdict is Pathogenic. Variant got 10 ACMG points: 10P and 0B. PVS1PM2
The NM_018100.4(EFHC1):c.883C>T(p.Gln295Ter) variant causes a stop gained change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as risk factor (no stars). Variant results in nonsense mediated mRNA decay.
Frequency
Genomes: not found (cov: 32)
Consequence
EFHC1
NM_018100.4 stop_gained
NM_018100.4 stop_gained
Scores
4
2
1
Clinical Significance
Conservation
PhyloP100: 4.55
Genes affected
EFHC1 (HGNC:16406): (EF-hand domain containing 1) This gene encodes an EF-hand-containing calcium binding protein. The encoded protein likely plays a role in calcium homeostasis. Mutations in this gene have been associated with susceptibility to juvenile myoclonic epilepsy and juvenile absence epilepsy. Alternatively spliced transcript variants have been described. [provided by RefSeq, Feb 2010]
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ACMG classification
Classification made for transcript
Verdict is Pathogenic. Variant got 10 ACMG points.
PVS1
?
Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
PM2
?
Very rare variant in population databases, with high coverage;
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
EFHC1 | NM_018100.4 | c.883C>T | p.Gln295Ter | stop_gained | 5/11 | ENST00000371068.11 | |
EFHC1 | NM_001172420.2 | c.826C>T | p.Gln276Ter | stop_gained | 6/12 | ||
EFHC1 | NR_033327.2 | n.2209C>T | non_coding_transcript_exon_variant | 4/10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
EFHC1 | ENST00000371068.11 | c.883C>T | p.Gln295Ter | stop_gained | 5/11 | 1 | NM_018100.4 | P1 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD3 genomes
?
Cov.:
32
GnomAD4 exome Cov.: 34
GnomAD4 exome
Cov.:
34
GnomAD4 genome ? Cov.: 32
GnomAD4 genome
?
Cov.:
32
ClinVar
Significance: risk factor
Submissions summary: Other:1
Revision: no assertion criteria provided
LINK: link
Submissions by phenotype
Myoclonic epilepsy, juvenile, susceptibility to, 1 Other:1
risk factor, no assertion criteria provided | literature only | OMIM | May 27, 2008 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
CADD
Pathogenic
DANN
Uncertain
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Uncertain
D
MutationTaster
Benign
A;A;A
Vest4
0.81, 0.81
GERP RS
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at