rs201019600

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_018460.4(ARHGAP15):​c.1199C>A​(p.Pro400Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P400L) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 31)

Consequence

ARHGAP15
NM_018460.4 missense

Scores

2
17

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.40
Variant links:
Genes affected
ARHGAP15 (HGNC:21030): (Rho GTPase activating protein 15) RHO GTPases (see ARHA; MIM 165390) regulate diverse biologic processes, and their activity is regulated by RHO GTPase-activating proteins (GAPs), such as ARHGAP15 (Seoh et al., 2003 [PubMed 12650940]).[supplied by OMIM, Mar 2008]
ARHGAP15-AS1 (HGNC:40949): (ARHGAP15 antisense RNA 1)

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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=0.1425603).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
ARHGAP15NM_018460.4 linkc.1199C>A p.Pro400Gln missense_variant Exon 13 of 14 ENST00000295095.11 NP_060930.3 Q53QZ3

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
ARHGAP15ENST00000295095.11 linkc.1199C>A p.Pro400Gln missense_variant Exon 13 of 14 1 NM_018460.4 ENSP00000295095.6 Q53QZ3
ARHGAP15ENST00000549436.5 linkn.361C>A non_coding_transcript_exon_variant Exon 4 of 4 3
ENSG00000257277ENST00000552220.1 linkn.206-26898G>T intron_variant Intron 1 of 1 4

Frequencies

GnomAD3 genomes
Cov.:
31
GnomAD4 exome
Cov.:
30
GnomAD4 genome
Cov.:
31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.067
BayesDel_addAF
Benign
-0.15
T
BayesDel_noAF
Benign
-0.46
CADD
Benign
19
DANN
Uncertain
0.98
DEOGEN2
Benign
0.046
T
Eigen
Benign
-0.074
Eigen_PC
Benign
0.11
FATHMM_MKL
Uncertain
0.80
D
LIST_S2
Benign
0.86
D
M_CAP
Benign
0.0050
T
MetaRNN
Benign
0.14
T
MetaSVM
Benign
-1.1
T
MutationAssessor
Benign
1.2
L
PrimateAI
Benign
0.33
T
PROVEAN
Benign
-0.50
N
REVEL
Benign
0.053
Sift
Benign
0.19
T
Sift4G
Benign
0.44
T
Polyphen
0.029
B
Vest4
0.39
MutPred
0.47
Loss of glycosylation at P400 (P = 0.0086);
MVP
0.39
MPC
0.057
ClinPred
0.53
D
GERP RS
5.3
Varity_R
0.17
gMVP
0.17

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr2-144461048; API