rs587777166
Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong
The NM_173728.4(ARHGEF15):c.1810C>T(p.Arg604Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000521 in 1,613,690 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts 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. R604H) has been classified as Uncertain significance.
Frequency
Consequence
NM_173728.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ARHGEF15 | NM_173728.4 | c.1810C>T | p.Arg604Cys | missense_variant | 11/16 | ENST00000361926.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ARHGEF15 | ENST00000361926.8 | c.1810C>T | p.Arg604Cys | missense_variant | 11/16 | 1 | NM_173728.4 | P1 | |
ARHGEF15 | ENST00000421050.2 | c.1810C>T | p.Arg604Cys | missense_variant | 11/16 | 1 | P1 | ||
ENST00000458568.1 | n.113G>A | non_coding_transcript_exon_variant | 1/2 | 3 | |||||
ARHGEF15 | ENST00000647883.1 | c.1273C>T | p.Arg425Cys | missense_variant | 8/13 |
Frequencies
GnomAD3 genomes AF: 0.0000263 AC: 4AN: 152112Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.000143 AC: 36AN: 251184Hom.: 0 AF XY: 0.0000810 AC XY: 11AN XY: 135780
GnomAD4 exome AF: 0.0000547 AC: 80AN: 1461578Hom.: 0 Cov.: 32 AF XY: 0.0000440 AC XY: 32AN XY: 727028
GnomAD4 genome AF: 0.0000263 AC: 4AN: 152112Hom.: 0 Cov.: 32 AF XY: 0.0000269 AC XY: 2AN XY: 74310
ClinVar
Submissions by phenotype
Early infantile epileptic encephalopathy with suppression bursts Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Jan 24, 2023 | 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 are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). ClinVar contains an entry for this variant (Variation ID: 100786). This missense change has been observed in individual(s) with epileptic encephalopathy (PMID: 23647072). The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This sequence change replaces arginine, which is basic and polar, with cysteine, which is neutral and slightly polar, at codon 604 of the ARHGEF15 protein (p.Arg604Cys). - |
not provided Uncertain:1
Uncertain significance, no assertion criteria provided | literature only | OMIM | Jul 01, 2013 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at