chr10-48450712-G-A
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Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_021226.4(ARHGAP22):c.1417C>T(p.Arg473Trp) variant causes a missense change. The variant allele was found at a frequency of 0.0000496 in 1,553,648 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.00023 ( 0 hom., cov: 34)
Exomes 𝑓: 0.000030 ( 1 hom. )
Consequence
ARHGAP22
NM_021226.4 missense
NM_021226.4 missense
Scores
3
8
8
Clinical Significance
Conservation
PhyloP100: 5.16
Genes affected
ARHGAP22 (HGNC:30320): (Rho GTPase activating protein 22) This gene encodes a member of the GTPase activating protein family which activates a GTPase belonging to the RAS superfamily of small GTP-binding proteins. The encoded protein is insulin-responsive, is dependent on the kinase Akt and requires the Akt-dependent 14-3-3 binding protein which binds sequentially to two serine residues. The result of these interactions is regulation of cell motility. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Dec 2011]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 0 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.19797277).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ARHGAP22 | NM_021226.4 | c.1417C>T | p.Arg473Trp | missense_variant | 9/10 | ENST00000249601.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ARHGAP22 | ENST00000249601.9 | c.1417C>T | p.Arg473Trp | missense_variant | 9/10 | 1 | NM_021226.4 | P4 |
Frequencies
GnomAD3 genomes AF: 0.000230 AC: 35AN: 152206Hom.: 0 Cov.: 34
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GnomAD3 exomes AF: 0.0000382 AC: 6AN: 157214Hom.: 0 AF XY: 0.0000120 AC XY: 1AN XY: 83602
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GnomAD4 exome AF: 0.0000300 AC: 42AN: 1401442Hom.: 1 Cov.: 36 AF XY: 0.0000304 AC XY: 21AN XY: 691628
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GnomAD4 genome AF: 0.000230 AC: 35AN: 152206Hom.: 0 Cov.: 34 AF XY: 0.000242 AC XY: 18AN XY: 74348
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Jan 17, 2023 | The c.1417C>T (p.R473W) alteration is located in exon 9 (coding exon 9) of the ARHGAP22 gene. This alteration results from a C to T substitution at nucleotide position 1417, causing the arginine (R) at amino acid position 473 to be replaced by a tryptophan (W). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Uncertain
DANN
Uncertain
DEOGEN2
Benign
T;T;T;.;.;.;.
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
LIST_S2
Pathogenic
D;D;D;D;D;D;D
M_CAP
Uncertain
D
MetaRNN
Benign
T;T;T;T;T;T;T
MetaSVM
Benign
T
MutationAssessor
Uncertain
M;.;.;.;.;.;.
MutationTaster
Benign
D;D;D;D;D;D;D
PrimateAI
Uncertain
T
PROVEAN
Pathogenic
D;D;D;D;D;D;D
REVEL
Benign
Sift
Pathogenic
D;D;D;D;D;D;D
Sift4G
Uncertain
D;D;D;D;D;D;D
Polyphen
D;D;.;.;D;.;B
Vest4
MVP
MPC
0.65
ClinPred
D
GERP RS
Varity_R
gMVP
Splicing
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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