chr10-48450712-G-A

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

Scores

3
8
8

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.16
Variant links:
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]

Genome browser will be placed here

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
ARHGAP22NM_021226.4 linkuse as main transcriptc.1417C>T p.Arg473Trp missense_variant 9/10 ENST00000249601.9

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
ARHGAP22ENST00000249601.9 linkuse as main transcriptc.1417C>T p.Arg473Trp missense_variant 9/101 NM_021226.4 P4Q7Z5H3-1

Frequencies

GnomAD3 genomes
AF:
0.000230
AC:
35
AN:
152206
Hom.:
0
Cov.:
34
show subpopulations
Gnomad AFR
AF:
0.000844
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000382
AC:
6
AN:
157214
Hom.:
0
AF XY:
0.0000120
AC XY:
1
AN XY:
83602
show subpopulations
Gnomad AFR exome
AF:
0.000457
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000165
Gnomad OTH exome
AF:
0.000227
GnomAD4 exome
AF:
0.0000300
AC:
42
AN:
1401442
Hom.:
1
Cov.:
36
AF XY:
0.0000304
AC XY:
21
AN XY:
691628
show subpopulations
Gnomad4 AFR exome
AF:
0.000691
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000126
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000102
Gnomad4 OTH exome
AF:
0.000120
GnomAD4 genome
AF:
0.000230
AC:
35
AN:
152206
Hom.:
0
Cov.:
34
AF XY:
0.000242
AC XY:
18
AN XY:
74348
show subpopulations
Gnomad4 AFR
AF:
0.000844
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000868
Hom.:
0
Bravo
AF:
0.000178
ExAC
AF:
0.0000442
AC:
5

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 submitterclinical testingAmbry GeneticsJan 17, 2023The 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: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.12
BayesDel_addAF
Benign
-0.34
T
BayesDel_noAF
Benign
-0.35
CADD
Uncertain
25
DANN
Uncertain
1.0
DEOGEN2
Benign
0.37
T;T;T;.;.;.;.
Eigen
Uncertain
0.42
Eigen_PC
Uncertain
0.35
FATHMM_MKL
Uncertain
0.88
D
LIST_S2
Pathogenic
0.98
D;D;D;D;D;D;D
M_CAP
Uncertain
0.090
D
MetaRNN
Benign
0.20
T;T;T;T;T;T;T
MetaSVM
Benign
-0.75
T
MutationAssessor
Uncertain
2.8
M;.;.;.;.;.;.
MutationTaster
Benign
1.0
D;D;D;D;D;D;D
PrimateAI
Uncertain
0.56
T
PROVEAN
Pathogenic
-5.7
D;D;D;D;D;D;D
REVEL
Benign
0.17
Sift
Pathogenic
0.0
D;D;D;D;D;D;D
Sift4G
Uncertain
0.0020
D;D;D;D;D;D;D
Polyphen
1.0
D;D;.;.;D;.;B
Vest4
0.45
MVP
0.51
MPC
0.65
ClinPred
0.79
D
GERP RS
4.4
Varity_R
0.41
gMVP
0.45

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.0
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs769696772; hg19: chr10-49658755; API