NM_012419.5:c.53C>T
Variant names:
Variant summary
Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_012419.5(RGS17):c.53C>T(p.Ala18Val) variant causes a missense change. The variant allele was found at a frequency of 0.0000031 in 1,612,986 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.000026 ( 0 hom., cov: 32)
Exomes 𝑓: 6.8e-7 ( 0 hom. )
Consequence
RGS17
NM_012419.5 missense
NM_012419.5 missense
Scores
4
15
Clinical Significance
Conservation
PhyloP100: 4.40
Publications
0 publications found
Genes affected
RGS17 (HGNC:14088): (regulator of G protein signaling 17) This gene encodes a member of the regulator of G-protein signaling family. This protein contains a conserved, 120 amino acid motif called the RGS domain and a cysteine-rich region. The protein attenuates the signaling activity of G-proteins by binding to activated, GTP-bound G alpha subunits and acting as a GTPase activating protein (GAP), increasing the rate of conversion of the GTP to GDP. This hydrolysis allows the G alpha subunits to bind G beta/gamma subunit heterodimers, forming inactive G-protein heterotrimers, thereby terminating the signal. [provided by RefSeq, Jul 2008]
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=0.19430459).
Transcripts
RefSeq
| Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|
| RGS17 | NM_012419.5 | c.53C>T | p.Ala18Val | missense_variant | Exon 2 of 5 | ENST00000206262.2 | NP_036551.3 | |
| RGS17 | XM_047418634.1 | c.98C>T | p.Ala33Val | missense_variant | Exon 2 of 5 | XP_047274590.1 | ||
| RGS17 | XM_047418635.1 | c.86C>T | p.Ala29Val | missense_variant | Exon 2 of 5 | XP_047274591.1 | ||
| RGS17 | XM_047418636.1 | c.53C>T | p.Ala18Val | missense_variant | Exon 2 of 5 | XP_047274592.1 |
Ensembl
Frequencies
GnomAD3 genomes 0.0000263 AC: 4AN: 152132Hom.: 0 Cov.: 32 show subpopulations
GnomAD3 genomes
AF:
AC:
4
AN:
152132
Hom.:
Cov.:
32
Gnomad AFR
AF:
Gnomad AMI
AF:
Gnomad AMR
AF:
Gnomad ASJ
AF:
Gnomad EAS
AF:
Gnomad SAS
AF:
Gnomad FIN
AF:
Gnomad MID
AF:
Gnomad NFE
AF:
Gnomad OTH
AF:
GnomAD4 exome AF: 6.85e-7 AC: 1AN: 1460854Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0AN XY: 726750 show subpopulations
GnomAD4 exome
AF:
AC:
1
AN:
1460854
Hom.:
Cov.:
31
AF XY:
AC XY:
0
AN XY:
726750
show subpopulations
African (AFR)
AF:
AC:
0
AN:
33358
American (AMR)
AF:
AC:
0
AN:
44576
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
26114
East Asian (EAS)
AF:
AC:
1
AN:
39564
South Asian (SAS)
AF:
AC:
0
AN:
86128
European-Finnish (FIN)
AF:
AC:
0
AN:
53414
Middle Eastern (MID)
AF:
AC:
0
AN:
5762
European-Non Finnish (NFE)
AF:
AC:
0
AN:
1111578
Other (OTH)
AF:
AC:
0
AN:
60360
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.525
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
GnomAD4 genome 0.0000263 AC: 4AN: 152132Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1AN XY: 74318 show subpopulations
GnomAD4 genome
AF:
AC:
4
AN:
152132
Hom.:
Cov.:
32
AF XY:
AC XY:
1
AN XY:
74318
show subpopulations
African (AFR)
AF:
AC:
2
AN:
41414
American (AMR)
AF:
AC:
1
AN:
15274
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
3470
East Asian (EAS)
AF:
AC:
0
AN:
5186
South Asian (SAS)
AF:
AC:
0
AN:
4828
European-Finnish (FIN)
AF:
AC:
0
AN:
10610
Middle Eastern (MID)
AF:
AC:
0
AN:
316
European-Non Finnish (NFE)
AF:
AC:
1
AN:
68034
Other (OTH)
AF:
AC:
0
AN:
2090
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.488
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
Alfa
AF:
Hom.:
Bravo
AF:
ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not specified Uncertain:1
Jul 13, 2022
Ambry Genetics
Significance:Uncertain significance
Review Status:criteria provided, single submitter
Collection Method:clinical testing
The c.53C>T (p.A18V) alteration is located in exon 2 (coding exon 1) of the RGS17 gene. This alteration results from a C to T substitution at nucleotide position 53, causing the alanine (A) at amino acid position 18 to be replaced by a valine (V). 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
DANN
Uncertain
DEOGEN2
Benign
T;T
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Uncertain
D
LIST_S2
Benign
.;T
M_CAP
Benign
T
MetaRNN
Benign
T;T
MetaSVM
Benign
T
MutationAssessor
Uncertain
M;M
PhyloP100
PrimateAI
Uncertain
T
PROVEAN
Benign
N;N
REVEL
Benign
Sift
Benign
T;T
Sift4G
Benign
T;T
Polyphen
P;P
Vest4
MutPred
Loss of relative solvent accessibility (P = 0.0404);Loss of relative solvent accessibility (P = 0.0404);
MVP
MPC
ClinPred
D
GERP RS
Varity_R
gMVP
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
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