6-52479251-G-A
Variant summary
Our verdict is Likely pathogenic. Variant got 8 ACMG points: 12P and 4B. PVS1PP3_StrongBS2
The NM_018100.4(EFHC1):c.1492+1G>A variant causes a splice donor change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000539 in 1,613,954 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. 3/3 splice prediction tools predicting alterations to normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Consequence
NM_018100.4 splice_donor
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_pathogenic. Variant got 8 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
EFHC1 | NM_018100.4 | c.1492+1G>A | splice_donor_variant | ENST00000371068.11 | |||
EFHC1 | NM_001172420.2 | c.1435+1G>A | splice_donor_variant | ||||
EFHC1 | NR_033327.2 | n.2818+1G>A | splice_donor_variant, non_coding_transcript_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
EFHC1 | ENST00000371068.11 | c.1492+1G>A | splice_donor_variant | 1 | NM_018100.4 | P1 |
Frequencies
GnomAD3 genomes AF: 0.0000197 AC: 3AN: 152180Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000279 AC: 7AN: 251318Hom.: 0 AF XY: 0.0000221 AC XY: 3AN XY: 135828
GnomAD4 exome AF: 0.0000575 AC: 84AN: 1461656Hom.: 0 Cov.: 32 AF XY: 0.0000564 AC XY: 41AN XY: 727148
GnomAD4 genome AF: 0.0000197 AC: 3AN: 152298Hom.: 0 Cov.: 32 AF XY: 0.0000134 AC XY: 1AN XY: 74468
ClinVar
Submissions by phenotype
Absence seizure;C1850778:Myoclonic epilepsy, juvenile, susceptibility to, 1 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Jun 07, 2021 | The current clinical and genetic evidence is not sufficient to establish whether loss-of-function variants in EFHC1 cause disease. Therefore, this variant has been classified as a Variant of Uncertain Significance. This variant is present in population databases (rs191404037, ExAC 0.004%) but has not been reported in the literature in individuals with an EFHC1-related disease. This sequence change affects a donor splice site in intron 8 of the EFHC1 gene. It is expected to disrupt RNA splicing and likely results in an absent or disrupted protein product. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at