6-153043966-G-A
Position:
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The ENST00000206262.2(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
ENST00000206262.2 missense
ENST00000206262.2 missense
Scores
4
15
Clinical Significance
Conservation
PhyloP100: 4.40
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 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=0.19430459).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
RGS17 | NM_012419.5 | c.53C>T | p.Ala18Val | missense_variant | 2/5 | ENST00000206262.2 | NP_036551.3 | |
RGS17 | XM_047418634.1 | c.98C>T | p.Ala33Val | missense_variant | 2/5 | XP_047274590.1 | ||
RGS17 | XM_047418635.1 | c.86C>T | p.Ala29Val | missense_variant | 2/5 | XP_047274591.1 | ||
RGS17 | XM_047418636.1 | c.53C>T | p.Ala18Val | missense_variant | 2/5 | XP_047274592.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
RGS17 | ENST00000206262.2 | c.53C>T | p.Ala18Val | missense_variant | 2/5 | 1 | NM_012419.5 | ENSP00000206262 | P1 | |
RGS17 | ENST00000367225.6 | c.53C>T | p.Ala18Val | missense_variant | 1/4 | 1 | ENSP00000356194 | P1 |
Frequencies
GnomAD3 genomes AF: 0.0000263 AC: 4AN: 152132Hom.: 0 Cov.: 32
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
GnomAD4 exome
AF:
AC:
1
AN:
1460854
Hom.:
Cov.:
31
AF XY:
AC XY:
0
AN XY:
726750
Gnomad4 AFR exome
AF:
Gnomad4 AMR exome
AF:
Gnomad4 ASJ exome
AF:
Gnomad4 EAS exome
AF:
Gnomad4 SAS exome
AF:
Gnomad4 FIN exome
AF:
Gnomad4 NFE exome
AF:
Gnomad4 OTH exome
AF:
GnomAD4 genome AF: 0.0000263 AC: 4AN: 152132Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1AN XY: 74318
GnomAD4 genome
AF:
AC:
4
AN:
152132
Hom.:
Cov.:
32
AF XY:
AC XY:
1
AN XY:
74318
Gnomad4 AFR
AF:
Gnomad4 AMR
AF:
Gnomad4 ASJ
AF:
Gnomad4 EAS
AF:
Gnomad4 SAS
AF:
Gnomad4 FIN
AF:
Gnomad4 NFE
AF:
Gnomad4 OTH
AF:
Bravo
AF:
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 | Jul 13, 2022 | 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
CADD
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
MutationTaster
Benign
D;D
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