8-53879428-G-A

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_Strong BP6_Moderate BP7 BA1

The NM_170587.4(RGS20):c.336G>A(p.Pro112=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0053 in 1,606,364 control chromosomes in the GnomAD database, including 377 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.029 (206 hom., cov: 32)
  • Exomes 𝑓: 0.0029 (171 hom.)
• Consequence: RGS20 NM_170587.4 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.37

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]

ACMG classification

Verdict is Benign. Variant got -15 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.68).
• BP6: Variant 8-53879428-G-A is Benign according to our data. Variant chr8-53879428-G-A is described in ClinVar as [Benign]. Clinvar id is 778397.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-1.37 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0962 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RGS20	NM_170587.4	c.336G>A	p.Pro112=	synonymous_variant	2/6	ENST00000297313.8
RGS20	NM_001286673.2	c.165+27364G>A		intron_variant
RGS20	NM_001286674.2	c.35+27364G>A		intron_variant
RGS20	NM_001286675.2	c.35+27364G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RGS20	ENST00000297313.8	c.336G>A	p.Pro112=	synonymous_variant	2/6	1	NM_170587.4
RGS20	ENST00000344277.10	c.165+27364G>A		intron_variant		1
RGS20	ENST00000517659.5	c.165+27364G>A		intron_variant, NMD_transcript_variant		1
RGS20	ENST00000523280.1	c.165+27364G>A		intron_variant, NMD_transcript_variant		1

Frequencies

GnomAD3 genomes AF: 0.0284 AC: 4315 AN: 152034 Hom.: 198 Cov.: 32

Gnomad AFR AF: 0.0979

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0121

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000828

Gnomad FIN AF: 0.0000942

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000353

Gnomad OTH AF: 0.0244

GnomAD3 exomes AF: 0.00657 AC: 1521 AN: 231510 Hom.: 62 AF XY: 0.00506 AC XY: 645 AN XY: 127428

Gnomad AFR exome AF: 0.0942

Gnomad AMR exome AF: 0.00655

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000167

Gnomad FIN exome AF: 0.0000489

Gnomad NFE exome AF: 0.000215

Gnomad OTH exome AF: 0.00460

GnomAD4 exome AF: 0.00286 AC: 4159 AN: 1454216 Hom.: 171 Cov.: 32 AF XY: 0.00256 AC XY: 1854 AN XY: 723392

Gnomad4 AFR exome AF: 0.0947

Gnomad4 AMR exome AF: 0.00726

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000291

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000182

Gnomad4 OTH exome AF: 0.00728

GnomAD4 genome AF: 0.0286 AC: 4357 AN: 152148 Hom.: 206 Cov.: 32 AF XY: 0.0273 AC XY: 2031 AN XY: 74380

Gnomad4 AFR AF: 0.0987

Gnomad4 AMR AF: 0.0120

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000414

Gnomad4 FIN AF: 0.0000942

Gnomad4 NFE AF: 0.000353

Gnomad4 OTH AF: 0.0241

Alfa AF: 0.00180 Hom.: 4

Bravo AF: 0.0317

Asia WGS AF: 0.0130 AC: 45 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jul 23, 2018

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.68
Cadd	Benign	1.0
Dann	Benign	0.90

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		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

Other links and lift over

dbSNP: rs75833547; hg19: chr8-54791988; COSMIC: COSV99033236; COSMIC: COSV99033236;