rs201263733
Variant summary
Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2
The NM_018100.4(EFHC1):āc.916A>Gā(p.Lys306Glu) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000105 in 1,614,088 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (ā ā ).
Frequency
Consequence
NM_018100.4 missense, splice_region
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -8 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
EFHC1 | NM_018100.4 | c.916A>G | p.Lys306Glu | missense_variant, splice_region_variant | 5/11 | ENST00000371068.11 | |
EFHC1 | NM_001172420.2 | c.859A>G | p.Lys287Glu | missense_variant, splice_region_variant | 6/12 | ||
EFHC1 | NR_033327.2 | n.2242A>G | splice_region_variant, non_coding_transcript_exon_variant | 4/10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
EFHC1 | ENST00000371068.11 | c.916A>G | p.Lys306Glu | missense_variant, splice_region_variant | 5/11 | 1 | NM_018100.4 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000197 AC: 3AN: 152212Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000358 AC: 9AN: 251320Hom.: 0 AF XY: 0.0000368 AC XY: 5AN XY: 135836
GnomAD4 exome AF: 0.00000958 AC: 14AN: 1461758Hom.: 0 Cov.: 34 AF XY: 0.0000124 AC XY: 9AN XY: 727186
GnomAD4 genome ? AF: 0.0000197 AC: 3AN: 152330Hom.: 0 Cov.: 32 AF XY: 0.0000134 AC XY: 1AN XY: 74498
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 20, 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 sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The glutamic acid amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. ClinVar contains an entry for this variant (Variation ID: 197833). This variant has not been reported in the literature in individuals affected with EFHC1-related conditions. This variant is present in population databases (rs201263733, gnomAD 0.05%). This sequence change replaces lysine, which is basic and polar, with glutamic acid, which is acidic and polar, at codon 306 of the EFHC1 protein (p.Lys306Glu). - |
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | Aug 21, 2014 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at