1-161049250-G-T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001025598.2(ARHGAP30):​c.1771C>A​(p.Leu591Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000205 in 1,461,822 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 31)
Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

ARHGAP30
NM_001025598.2 missense

Scores

2
17

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.47

Publications

38 publications found
Variant links:
Genes affected
ARHGAP30 (HGNC:27414): (Rho GTPase activating protein 30) Predicted to enable GTPase activator activity. Predicted to be involved in small GTPase mediated signal transduction. Located in intracellular membrane-bounded organelle. [provided by Alliance of Genome Resources, Apr 2022]

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.09091857).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
ARHGAP30NM_001025598.2 linkc.1771C>A p.Leu591Met missense_variant Exon 12 of 12 ENST00000368013.8 NP_001020769.1 Q7Z6I6-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
ARHGAP30ENST00000368013.8 linkc.1771C>A p.Leu591Met missense_variant Exon 12 of 12 2 NM_001025598.2 ENSP00000356992.3 Q7Z6I6-1

Frequencies

GnomAD3 genomes
Cov.:
31
GnomAD2 exomes
AF:
0.0000120
AC:
3
AN:
250080
AF XY:
0.0000148
show subpopulations
Gnomad AFR exome
AF:
0.0000617
Gnomad AMR exome
AF:
0.0000289
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00000889
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000205
AC:
3
AN:
1461822
Hom.:
0
Cov.:
89
AF XY:
0.00000413
AC XY:
3
AN XY:
727206
show subpopulations
African (AFR)
AF:
0.00
AC:
0
AN:
33480
American (AMR)
AF:
0.0000224
AC:
1
AN:
44724
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
26136
East Asian (EAS)
AF:
0.00
AC:
0
AN:
39700
South Asian (SAS)
AF:
0.00
AC:
0
AN:
86258
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
53376
Middle Eastern (MID)
AF:
0.000173
AC:
1
AN:
5768
European-Non Finnish (NFE)
AF:
8.99e-7
AC:
1
AN:
1111994
Other (OTH)
AF:
0.00
AC:
0
AN:
60386
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.492
Heterozygous variant carriers
0
1
1
2
2
3
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Exome Het
Variant carriers
0
2
4
6
8
10
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
GnomAD4 genome
Cov.:
31
Alfa
AF:
0.0000206
Hom.:
8276
ExAC
AF:
0.00000824
AC:
1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.097
BayesDel_addAF
Benign
-0.26
T
BayesDel_noAF
Benign
-0.53
CADD
Benign
14
DANN
Uncertain
0.99
DEOGEN2
Benign
0.018
.;T;.
Eigen
Benign
-0.056
Eigen_PC
Benign
-0.12
FATHMM_MKL
Benign
0.61
D
LIST_S2
Benign
0.77
T;T;T
M_CAP
Benign
0.0083
T
MetaRNN
Benign
0.091
T;T;T
MetaSVM
Benign
-1.1
T
MutationAssessor
Benign
0.55
.;N;.
PhyloP100
1.5
PrimateAI
Benign
0.30
T
PROVEAN
Benign
-0.050
N;N;N
REVEL
Benign
0.14
Sift
Uncertain
0.027
D;D;T
Sift4G
Benign
0.25
T;T;T
Polyphen
0.92
.;P;.
Vest4
0.12
MutPred
0.083
Gain of solvent accessibility (P = 0.019);Gain of solvent accessibility (P = 0.019);.;
MVP
0.19
MPC
0.16
ClinPred
0.14
T
GERP RS
1.1
Varity_R
0.066
gMVP
0.11
Mutation Taster
=96/4
polymorphism

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.010
Details are displayed if max score is > 0.2

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

Publications

Other links and lift over

dbSNP: rs3813609; hg19: chr1-161019040; API