1-163074342-A-T
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Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_005613.6(RGS4):c.400A>T(p.Arg134Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000031 in 1,613,722 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 0.000013 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0000021 ( 0 hom. )
Consequence
RGS4
NM_005613.6 missense
NM_005613.6 missense
Scores
4
5
7
Clinical Significance
Conservation
PhyloP100: 1.17
Genes affected
RGS4 (HGNC:10000): (regulator of G protein signaling 4) Regulator of G protein signaling (RGS) family members are regulatory molecules that act as GTPase activating proteins (GAPs) for G alpha subunits of heterotrimeric G proteins. RGS proteins are able to deactivate G protein subunits of the Gi alpha, Go alpha and Gq alpha subtypes. They drive G proteins into their inactive GDP-bound forms. Regulator of G protein signaling 4 belongs to this family. All RGS proteins share a conserved 120-amino acid sequence termed the RGS domain. Regulator of G protein signaling 4 protein is 37% identical to RGS1 and 97% identical to rat Rgs4. This protein negatively regulate signaling upstream or at the level of the heterotrimeric G protein and is localized in the cytoplasm. Alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Jul 2008]
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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=0.2279019).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
RGS4 | NM_005613.6 | c.400A>T | p.Arg134Trp | missense_variant | 5/5 | ENST00000367909.11 | NP_005604.1 | |
RGS4 | NM_001102445.3 | c.691A>T | p.Arg231Trp | missense_variant | 6/6 | NP_001095915.1 | ||
RGS4 | NM_001113380.1 | c.346A>T | p.Arg116Trp | missense_variant | 5/5 | NP_001106851.1 | ||
RGS4 | NM_001113381.1 | c.233A>T | p.Gln78Leu | missense_variant | 4/4 | NP_001106852.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
RGS4 | ENST00000367909.11 | c.400A>T | p.Arg134Trp | missense_variant | 5/5 | 1 | NM_005613.6 | ENSP00000356885 | P1 |
Frequencies
GnomAD3 genomes AF: 0.0000131 AC: 2AN: 152180Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.00000398 AC: 1AN: 251140Hom.: 0 AF XY: 0.00000737 AC XY: 1AN XY: 135748
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GnomAD4 exome AF: 0.00000205 AC: 3AN: 1461542Hom.: 0 Cov.: 31 AF XY: 0.00000275 AC XY: 2AN XY: 727088
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GnomAD4 genome AF: 0.0000131 AC: 2AN: 152180Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1AN XY: 74340
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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 | Aug 17, 2021 | The c.691A>T (p.R231W) alteration is located in exon 6 (coding exon 6) of the RGS4 gene. This alteration results from a A to T substitution at nucleotide position 691, causing the arginine (R) at amino acid position 231 to be replaced by a tryptophan (W). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Uncertain
T
BayesDel_noAF
Pathogenic
CADD
Uncertain
DANN
Uncertain
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
LIST_S2
Benign
T
M_CAP
Benign
D
MetaRNN
Benign
T
MetaSVM
Benign
T
MutationTaster
Benign
D;D;D;D;D;N
PROVEAN
Benign
N
REVEL
Benign
Sift
Pathogenic
D
Sift4G
Pathogenic
D
Vest4
MVP
ClinPred
D
GERP RS
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