5-73752992-G-C
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_001177693.2(ARHGEF28):c.265G>C(p.Val89Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000197 in 152,228 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 (★). Synonymous variant affecting the same amino acid position (i.e. V89V) has been classified as Benign.
Frequency
Consequence
NM_001177693.2 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 0 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ARHGEF28 | NM_001177693.2 | c.265G>C | p.Val89Leu | missense_variant | 4/36 | ENST00000513042.7 | |
ARHGEF28 | NM_001080479.3 | c.265G>C | p.Val89Leu | missense_variant | 4/37 | ||
ARHGEF28 | NM_001388078.1 | c.265G>C | p.Val89Leu | missense_variant | 4/35 | ||
ARHGEF28 | NM_001388076.1 | c.181+3008G>C | intron_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ARHGEF28 | ENST00000513042.7 | c.265G>C | p.Val89Leu | missense_variant | 4/36 | 5 | NM_001177693.2 |
Frequencies
GnomAD3 genomes ? AF: 0.0000197 AC: 3AN: 152228Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.00000403 AC: 1AN: 248172Hom.: 0 AF XY: 0.00000743 AC XY: 1AN XY: 134602
GnomAD4 exome Cov.: 31
GnomAD4 genome ? AF: 0.0000197 AC: 3AN: 152228Hom.: 0 Cov.: 32 AF XY: 0.0000269 AC XY: 2AN XY: 74362
ClinVar
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Oct 29, 2021 | The c.265G>C (p.V89L) alteration is located in exon 4 (coding exon 3) of the ARHGEF28 gene. This alteration results from a G to C substitution at nucleotide position 265, causing the valine (V) at amino acid position 89 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at