chr8-53958454-C-T
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Variant summary
Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2
The NM_170587.4(RGS20):c.1163C>T(p.Ala388Val) variant causes a missense change. The variant allele was found at a frequency of 0.0000172 in 1,453,822 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 0.000020 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000017 ( 0 hom. )
Consequence
RGS20
NM_170587.4 missense
NM_170587.4 missense
Scores
8
11
Clinical Significance
Conservation
PhyloP100: 4.38
Genes affected
RGS20 (HGNC:14600): (regulator of G protein signaling 20) The protein encoded by this gene belongs to the family of regulator of G protein signaling (RGS) proteins, which are regulatory and structural components of G protein-coupled receptor complexes. RGS proteins inhibit signal transduction by increasing the GTPase activity of G protein alpha subunits, thereby driving them into their inactive GDP-bound forms. This protein selectively binds to G(z)-alpha and G(alpha)-i2 subunits, and regulates their signaling activities. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Sep 2011]
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ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -6 ACMG points.
BP4
Computational evidence support a benign effect (MetaRNN=0.18090698).
BS2
High AC in GnomAdExome4 at 22 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
RGS20 | NM_170587.4 | c.1163C>T | p.Ala388Val | missense_variant | 6/6 | ENST00000297313.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
RGS20 | ENST00000297313.8 | c.1163C>T | p.Ala388Val | missense_variant | 6/6 | 1 | NM_170587.4 |
Frequencies
GnomAD3 genomes AF: 0.0000197 AC: 3AN: 151966Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.00000617 AC: 1AN: 162182Hom.: 0 AF XY: 0.0000112 AC XY: 1AN XY: 89586
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GnomAD4 exome AF: 0.0000169 AC: 22AN: 1301856Hom.: 0 Cov.: 24 AF XY: 0.00000622 AC XY: 4AN XY: 642702
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GnomAD4 genome AF: 0.0000197 AC: 3AN: 151966Hom.: 0 Cov.: 32 AF XY: 0.0000269 AC XY: 2AN XY: 74252
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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 | Mar 29, 2023 | The c.1163C>T (p.A388V) alteration is located in exon 6 (coding exon 6) of the RGS20 gene. This alteration results from a C to T substitution at nucleotide position 1163, causing the alanine (A) at amino acid position 388 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;.;.;.
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
LIST_S2
Uncertain
D;D;D;D
M_CAP
Benign
T
MetaRNN
Benign
T;T;T;T
MetaSVM
Benign
T
MutationAssessor
Benign
L;.;.;.
MutationTaster
Benign
D;D;D;D
PrimateAI
Benign
T
PROVEAN
Uncertain
D;D;D;D
REVEL
Benign
Sift
Uncertain
D;D;D;D
Sift4G
Uncertain
D;D;D;D
Polyphen
P;P;.;P
Vest4
MutPred
Gain of methylation at K384 (P = 0.1089);.;.;.;
MVP
MPC
ClinPred
D
GERP RS
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gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at