6-129618731-C-T
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Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_033515.3(ARHGAP18):c.908G>A(p.Gly303Asp) variant causes a missense change. The variant allele was found at a frequency of 0.000018 in 1,613,258 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.00011 ( 0 hom., cov: 31)
Exomes 𝑓: 0.0000089 ( 0 hom. )
Consequence
ARHGAP18
NM_033515.3 missense
NM_033515.3 missense
Scores
10
7
Clinical Significance
Conservation
PhyloP100: 4.36
Genes affected
ARHGAP18 (HGNC:21035): (Rho GTPase activating protein 18) Enables GTPase activator activity. Involved in several processes, including regulation of actin filament polymerization; regulation of small GTPase mediated signal transduction; and small GTPase mediated signal transduction. Located in cytosol; nuclear speck; and plasma membrane. Part of cytoplasmic microtubule and ruffle. Implicated in schizophrenia. [provided by Alliance of Genome Resources, Apr 2022]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 2 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
ARHGAP18 | NM_033515.3 | c.908G>A | p.Gly303Asp | missense_variant | 6/15 | ENST00000368149.3 | NP_277050.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
ARHGAP18 | ENST00000368149.3 | c.908G>A | p.Gly303Asp | missense_variant | 6/15 | 1 | NM_033515.3 | ENSP00000357131 | P1 |
Frequencies
GnomAD3 genomes AF: 0.000105 AC: 16AN: 152110Hom.: 0 Cov.: 31
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GnomAD3 exomes AF: 0.0000200 AC: 5AN: 249946Hom.: 0 AF XY: 0.00000738 AC XY: 1AN XY: 135548
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GnomAD4 exome AF: 0.00000890 AC: 13AN: 1461030Hom.: 0 Cov.: 30 AF XY: 0.00000413 AC XY: 3AN XY: 726778
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GnomAD4 genome AF: 0.000105 AC: 16AN: 152228Hom.: 0 Cov.: 31 AF XY: 0.0000941 AC XY: 7AN XY: 74420
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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 | Aug 16, 2022 | The c.908G>A (p.G303D) alteration is located in exon 6 (coding exon 6) of the ARHGAP18 gene. This alteration results from a G to A substitution at nucleotide position 908, causing the glycine (G) at amino acid position 303 to be replaced by an aspartic acid (D). 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
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
LIST_S2
Uncertain
D
M_CAP
Benign
T
MetaRNN
Uncertain
D
MetaSVM
Benign
T
MutationAssessor
Uncertain
M
MutationTaster
Benign
D;D
PrimateAI
Uncertain
T
REVEL
Uncertain
Sift4G
Uncertain
T
Polyphen
P
Vest4
MVP
MPC
ClinPred
T
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
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