chr6-52469342-C-T
Variant summary
Our verdict is Likely benign. Variant got -3 ACMG points: 1P and 4B. PP3BS2
The NM_018100.4(EFHC1):c.1147C>T(p.Pro383Ser) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000341 in 1,613,970 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Consequence
NM_018100.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -3 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
EFHC1 | NM_018100.4 | c.1147C>T | p.Pro383Ser | missense_variant | Exon 7 of 11 | ENST00000371068.11 | NP_060570.2 | |
EFHC1 | NM_001172420.2 | c.1090C>T | p.Pro364Ser | missense_variant | Exon 8 of 12 | NP_001165891.1 | ||
EFHC1 | NR_033327.2 | n.2473C>T | non_coding_transcript_exon_variant | Exon 6 of 10 |
Ensembl
Frequencies
GnomAD3 genomes AF: 0.0000263 AC: 4AN: 152156Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000279 AC: 7AN: 251342Hom.: 0 AF XY: 0.0000221 AC XY: 3AN XY: 135836
GnomAD4 exome AF: 0.0000349 AC: 51AN: 1461696Hom.: 0 Cov.: 30 AF XY: 0.0000289 AC XY: 21AN XY: 727142
GnomAD4 genome AF: 0.0000263 AC: 4AN: 152274Hom.: 0 Cov.: 32 AF XY: 0.0000134 AC XY: 1AN XY: 74464
ClinVar
Submissions by phenotype
Myoclonic epilepsy, juvenile, susceptibility to, 1;C5551411:Typical absence seizure Uncertain:1
This sequence change replaces proline, which is neutral and non-polar, with serine, which is neutral and polar, at codon 383 of the EFHC1 protein (p.Pro383Ser). This variant is present in population databases (rs546262142, gnomAD 0.01%). This variant has not been reported in the literature in individuals affected with EFHC1-related conditions. This missense change has been observed in at least one individual who was not affected with EFHC1-related conditions (Invitae). ClinVar contains an entry for this variant (Variation ID: 534110). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive. 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. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at