8-99962943-T-C

Variant summary

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

The NM_015668.5(RGS22):c.3651A>G(p.Leu1217=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00495 in 1,596,860 control chromosomes in the GnomAD database, including 298 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.027 (157 hom., cov: 32)
  • Exomes 𝑓: 0.0026 (141 hom.)
• Consequence: RGS22 NM_015668.5 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.359

Genes affected

RGS22 (HGNC:24499): (regulator of G protein signaling 22) Enables G-protein alpha-subunit binding activity. Predicted to be involved in negative regulation of signal transduction. Located in actin cytoskeleton; cytosol; and fibrillar center. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -15 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.56).
• BP6: Variant 8-99962943-T-C is Benign according to our data. Variant chr8-99962943-T-C is described in ClinVar as [Benign]. Clinvar id is 776366.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=0.359 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0893 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RGS22	NM_015668.5	c.3651A>G	p.Leu1217=	synonymous_variant	25/28	ENST00000360863.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RGS22	ENST00000360863.11	c.3651A>G	p.Leu1217=	synonymous_variant	25/28	1	NM_015668.5	P3

Frequencies

GnomAD3 genomes AF: 0.0269 AC: 4089 AN: 152182 Hom.: 157 Cov.: 32

Gnomad AFR AF: 0.0918

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0141

Gnomad ASJ AF: 0.00202

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000622

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0285

Gnomad NFE AF: 0.000309

Gnomad OTH AF: 0.0144

GnomAD3 exomes AF: 0.00699 AC: 1612 AN: 230740 Hom.: 64 AF XY: 0.00557 AC XY: 697 AN XY: 125158

Gnomad AFR exome AF: 0.0933

Gnomad AMR exome AF: 0.00521

Gnomad ASJ exome AF: 0.000997

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000388

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000222

Gnomad OTH exome AF: 0.00399

GnomAD4 exome AF: 0.00264 AC: 3816 AN: 1444560 Hom.: 141 Cov.: 31 AF XY: 0.00237 AC XY: 1699 AN XY: 717952

Gnomad4 AFR exome AF: 0.0933

Gnomad4 AMR exome AF: 0.00567

Gnomad4 ASJ exome AF: 0.00130

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000111

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000164

Gnomad4 OTH exome AF: 0.00590

GnomAD4 genome AF: 0.0269 AC: 4096 AN: 152300 Hom.: 157 Cov.: 32 AF XY: 0.0263 AC XY: 1958 AN XY: 74484

Gnomad4 AFR AF: 0.0917

Gnomad4 AMR AF: 0.0141

Gnomad4 ASJ AF: 0.00202

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000415

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000309

Gnomad4 OTH AF: 0.0142

Alfa AF: 0.0122 Hom.: 50

Bravo AF: 0.0304

Asia WGS AF: 0.00636 AC: 22 AN: 3472

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

Dec 31, 2019

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.56
Cadd	Benign	6.5
Dann	Benign	0.72

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: rs73699897; hg19: chr8-100975171;