chr6-52452751-A-T
Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4
The NM_018100.4(EFHC1):c.637A>T(p.Thr213Ser) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000186 in 1,614,088 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. T213A) has been classified as Uncertain significance.
Frequency
Consequence
NM_018100.4 missense
Scores
Clinical Significance
Conservation
Genome browser will be placed here
ACMG classification
Verdict is Uncertain_significance. Variant got 1 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
EFHC1 | NM_018100.4 | c.637A>T | p.Thr213Ser | missense_variant | 4/11 | ENST00000371068.11 | |
EFHC1 | NM_001172420.2 | c.580A>T | p.Thr194Ser | missense_variant | 5/12 | ||
EFHC1 | NR_033327.2 | n.706A>T | non_coding_transcript_exon_variant | 4/10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
EFHC1 | ENST00000371068.11 | c.637A>T | p.Thr213Ser | missense_variant | 4/11 | 1 | NM_018100.4 | P1 |
Frequencies
GnomAD3 genomes AF: 0.0000131 AC: 2AN: 152222Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.00000795 AC: 2AN: 251428Hom.: 0 AF XY: 0.00000736 AC XY: 1AN XY: 135874
GnomAD4 exome AF: 6.84e-7 AC: 1AN: 1461866Hom.: 0 Cov.: 32 AF XY: 0.00000138 AC XY: 1AN XY: 727232
GnomAD4 genome AF: 0.0000131 AC: 2AN: 152222Hom.: 0 Cov.: 32 AF XY: 0.0000134 AC XY: 1AN XY: 74362
ClinVar
Submissions by phenotype
Absence seizure;C1850778:Myoclonic epilepsy, juvenile, susceptibility to, 1 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Mar 23, 2022 | 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. 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 tolerated. ClinVar contains an entry for this variant (Variation ID: 567935). This variant has not been reported in the literature in individuals affected with EFHC1-related conditions. This variant is present in population databases (no rsID available, gnomAD 0.009%). This sequence change replaces threonine, which is neutral and polar, with serine, which is neutral and polar, at codon 213 of the EFHC1 protein (p.Thr213Ser). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at