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GeneBe

6-153011669-T-C

Variant summary

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

The NM_012419.5(RGS17):c.538A>G(p.Thr180Ala) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000136 in 1,612,388 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 0.000039 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000011 ( 0 hom. )

Consequence

RGS17
NM_012419.5 missense

Scores

5
6
7

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.98
Variant links:
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=0.18701449).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
RGS17NM_012419.5 linkuse as main transcriptc.538A>G p.Thr180Ala missense_variant 5/5 ENST00000206262.2
RGS17XM_047418634.1 linkuse as main transcriptc.583A>G p.Thr195Ala missense_variant 5/5
RGS17XM_047418635.1 linkuse as main transcriptc.571A>G p.Thr191Ala missense_variant 5/5
RGS17XM_047418636.1 linkuse as main transcriptc.538A>G p.Thr180Ala missense_variant 5/5

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
RGS17ENST00000206262.2 linkuse as main transcriptc.538A>G p.Thr180Ala missense_variant 5/51 NM_012419.5 P1
RGS17ENST00000367225.6 linkuse as main transcriptc.538A>G p.Thr180Ala missense_variant 4/41 P1

Frequencies

GnomAD3 genomes
AF:
0.0000394
AC:
6
AN:
152222
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00115
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000758
AC:
19
AN:
250810
Hom.:
0
AF XY:
0.0000811
AC XY:
11
AN XY:
135634
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00103
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000110
AC:
16
AN:
1460048
Hom.:
0
Cov.:
29
AF XY:
0.00000964
AC XY:
7
AN XY:
726392
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.000379
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.0000166
GnomAD4 genome
AF:
0.0000394
AC:
6
AN:
152340
Hom.:
0
Cov.:
32
AF XY:
0.0000537
AC XY:
4
AN XY:
74492
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00116
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.0000189
ExAC
AF:
0.0000659
AC:
8

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 submitterclinical testingAmbry GeneticsAug 21, 2023The c.538A>G (p.T180A) alteration is located in exon 5 (coding exon 4) of the RGS17 gene. This alteration results from a A to G substitution at nucleotide position 538, causing the threonine (T) at amino acid position 180 to be replaced by an alanine (A). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
0.81
BayesDel_addAF
Benign
-0.23
T
BayesDel_noAF
Benign
-0.16
Cadd
Uncertain
24
Dann
Uncertain
1.0
DEOGEN2
Benign
0.34
T;T
Eigen
Pathogenic
0.77
Eigen_PC
Pathogenic
0.73
FATHMM_MKL
Pathogenic
0.98
D
M_CAP
Benign
0.015
T
MetaRNN
Benign
0.19
T;T
MetaSVM
Benign
-1.1
T
MutationAssessor
Uncertain
2.1
M;M
MutationTaster
Benign
1.0
D;D
PrimateAI
Uncertain
0.75
T
PROVEAN
Pathogenic
-4.9
D;D
REVEL
Uncertain
0.39
Sift
Uncertain
0.019
D;D
Sift4G
Uncertain
0.026
D;D
Polyphen
0.99
D;D
Vest4
0.55
MutPred
0.49
Gain of helix (P = 0.132);Gain of helix (P = 0.132);
MVP
0.61
MPC
0.50
ClinPred
0.34
T
GERP RS
5.2
Varity_R
0.82
gMVP
0.35

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.020
Details are displayed if max score is > 0.2

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs556779833; hg19: chr6-153332804; API