rs587776969
Positions:
Variant summary
Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM1PM2PM4_SupportingPP5
The NM_004309.6(ARHGDIA):c.553_555del(p.Asp185del) variant causes a inframe deletion change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Pathogenic (no stars).
Frequency
Genomes: not found (cov: 32)
Exomes 𝑓: 0.0 ( 0 hom. )
Failed GnomAD Quality Control
Consequence
ARHGDIA
NM_004309.6 inframe_deletion
NM_004309.6 inframe_deletion
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 7.50
Genes affected
ARHGDIA (HGNC:678): (Rho GDP dissociation inhibitor alpha) This gene encodes a protein that plays a key role in the regulation of signaling through Rho GTPases. The encoded protein inhibits the disassociation of Rho family members from GDP (guanine diphosphate), thereby maintaining these factors in an inactive state. Activity of this protein is important in a variety of cellular processes, and expression of this gene may be altered in tumors. Mutations in this gene have been found in individuals with nephrotic syndrome, type 8. Alternate splicing results in multiple transcript variants. [provided by RefSeq, Jul 2014]
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ACMG classification
Classification made for transcript
Verdict is Likely_pathogenic. Variant got 6 ACMG points.
PM1
?
In a mutagenesis_site Loss of RHOA interaction; when associated with A-45. (size 0) in uniprot entity GDIR1_HUMAN
PM2
?
Very rare variant in population databases, with high coverage;
PM4
?
Nonframeshift variant in NON repetitive region in NM_004309.6. Strenght limited to Supporting due to length of the change: 1aa.
PP5
?
Variant 17-81868935-TGTC-T is Pathogenic according to our data. Variant chr17-81868935-TGTC-T is described in ClinVar as [Pathogenic]. Clinvar id is 50501.Status of the report is no_assertion_criteria_provided, 0 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ARHGDIA | NM_004309.6 | c.553_555del | p.Asp185del | inframe_deletion | 6/6 | ENST00000269321.12 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ARHGDIA | ENST00000269321.12 | c.553_555del | p.Asp185del | inframe_deletion | 6/6 | 1 | NM_004309.6 | P1 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD3 genomes
?
Cov.:
32
GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0AN: 1461604Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 727092
GnomAD4 exome
Data not reliable, filtered out with message: AC0
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1461604
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0
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727092
Gnomad4 AFR exome
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GnomAD4 genome ? Cov.: 32
GnomAD4 genome
?
Cov.:
32
ClinVar
Significance: Pathogenic
Submissions summary: Pathogenic:1
Revision: no assertion criteria provided
LINK: link
Submissions by phenotype
Nephrotic syndrome, type 8 Pathogenic:1
Pathogenic, no assertion criteria provided | literature only | OMIM | May 01, 2013 | - - |
Computational scores
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at