chr6-52452791-CATCAGACTTTG-C
Variant summary
Our verdict is Uncertain significance. Variant got 4 ACMG points: 8P and 4B. PVS1BS2
The NM_018100.4(EFHC1):c.682_692delGACTTTGATCA(p.Asp228ThrfsTer8) variant causes a frameshift change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000496 in 1,614,050 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★★). Variant results in nonsense mediated mRNA decay.
Frequency
Consequence
NM_018100.4 frameshift
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 4 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
EFHC1 | NM_018100.4 | c.682_692delGACTTTGATCA | p.Asp228ThrfsTer8 | frameshift_variant | Exon 4 of 11 | ENST00000371068.11 | NP_060570.2 | |
EFHC1 | NM_001172420.2 | c.625_635delGACTTTGATCA | p.Asp209ThrfsTer8 | frameshift_variant | Exon 5 of 12 | NP_001165891.1 | ||
EFHC1 | NR_033327.2 | n.751_761delGACTTTGATCA | non_coding_transcript_exon_variant | Exon 4 of 10 |
Ensembl
Frequencies
GnomAD3 genomes AF: 0.0000526 AC: 8AN: 152194Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000358 AC: 9AN: 251442Hom.: 0 AF XY: 0.0000221 AC XY: 3AN XY: 135882
GnomAD4 exome AF: 0.0000493 AC: 72AN: 1461856Hom.: 0 AF XY: 0.0000536 AC XY: 39AN XY: 727230
GnomAD4 genome AF: 0.0000526 AC: 8AN: 152194Hom.: 0 Cov.: 32 AF XY: 0.0000403 AC XY: 3AN XY: 74360
ClinVar
Submissions by phenotype
Absence seizure;C1850778:Myoclonic epilepsy, juvenile, susceptibility to, 1 Uncertain:2
This variant has not been reported in the literature in individuals with EFHC1-related conditions. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. The current clinical and genetic evidence is not sufficient to establish whether loss-of-function variants in EFHC1 cause disease. The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the ExAC database. This sequence change creates a premature translational stop signal (p.Asp228Thrfs*8) in the EFHC1 gene. It is expected to result in an absent or disrupted protein product. -
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not provided Uncertain:1
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Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at