8-99981942-C-T

Variant names:

• chr8-99981942-C-T
• rs200869556
• NM_015668.5:c.3355G>A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_015668.5(RGS22):​c.3355G>A​(p.Ala1119Thr) variant causes a missense change. The variant allele was found at a frequency of 0.0000305 in 1,607,584 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00018 (0 hom., cov: 31)
  • Exomes 𝑓: 0.000015 (0 hom.)
• Consequence: RGS22 NM_015668.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.17
• Publications: 1 publications found

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

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015668.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RGS22	NM_015668.5	MANE Select	c.3355G>A	p.Ala1119Thr	missense	Exon 22 of 28	NP_056483.3	Q8NE09-1
	RGS22	NM_001286692.2		c.3319G>A	p.Ala1107Thr	missense	Exon 22 of 28	NP_001273621.1	Q8NE09-3
	RGS22	NM_001286693.2		c.2812G>A	p.Ala938Thr	missense	Exon 20 of 26	NP_001273622.1	G3V112

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RGS22	ENST00000360863.11	TSL:1 MANE Select	c.3355G>A	p.Ala1119Thr	missense	Exon 22 of 28	ENSP00000354109.6	Q8NE09-1
	RGS22	ENST00000523437.5	TSL:1	c.3319G>A	p.Ala1107Thr	missense	Exon 22 of 28	ENSP00000428212.1	Q8NE09-3
	RGS22	ENST00000870307.1		c.3196G>A	p.Ala1066Thr	missense	Exon 21 of 27	ENSP00000540366.1

Frequencies

GnomAD3 genomes AF: 0.000178 AC: 27 AN: 151988 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.000580

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000197

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

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

GnomAD2 exomes AF: 0.0000452 AC: 11 AN: 243298 AF XY: 0.0000227

Gnomad AFR exome AF: 0.000527

Gnomad AMR exome AF: 0.0000302

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.000340

GnomAD4 exome AF: 0.0000151 AC: 22 AN: 1455478 Hom.: 0 Cov.: 30 AF XY: 0.00000967 AC XY: 7 AN XY: 723938

African (AFR) AF: 0.000393 AC: 13 AN: 33080

American (AMR) AF: 0.0000917 AC: 4 AN: 43602

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25898

East Asian (EAS) AF: 0.00 AC: 0 AN: 39356

South Asian (SAS) AF: 0.0000118 AC: 1 AN: 85002

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53310

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5742

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1109404

Other (OTH) AF: 0.0000666 AC: 4 AN: 60084

GnomAD4 genome AF: 0.000178 AC: 27 AN: 152106 Hom.: 0 Cov.: 31 AF XY: 0.000108 AC XY: 8 AN XY: 74356

African (AFR) AF: 0.000578 AC: 24 AN: 41512

American (AMR) AF: 0.000196 AC: 3 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5162

South Asian (SAS) AF: 0.00 AC: 0 AN: 4810

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10572

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67982

Other (OTH) AF: 0.00 AC: 0 AN: 2112

Alfa AF: 0.0000784 Hom.: 0

Bravo AF: 0.000219

ESP6500AA AF: 0.000521 AC: 2

ESP6500EA AF: 0.00 AC: 0

ExAC AF: 0.0000414 AC: 5

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.47
BayesDel_addAF	Benign	-0.038	T
BayesDel_noAF	Uncertain	0.040
CADD	Pathogenic	27
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.062	T
Eigen	Pathogenic	0.73
Eigen_PC	Pathogenic	0.71
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.92	D
M_CAP	Uncertain	0.097	D
MetaRNN	Uncertain	0.58	D
MetaSVM	Benign	-1.2	T
MutationAssessor	Uncertain	2.3	M
PhyloP100		7.2
PrimateAI	Uncertain	0.64	T
PROVEAN	Uncertain	-3.3	D
REVEL	Uncertain	0.42
Sift	Uncertain	0.0050	D
Sift4G	Pathogenic	0.0	D
Polyphen		1.0	D
Vest4		0.89
MVP		0.48
MPC		0.35
ClinPred		0.66	D
GERP RS		5.0
Varity_R		0.55
gMVP		0.70
Mutation Taster		=46/54	disease causing

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

Other links and lift over

dbSNP: rs200869556; hg19: chr8-100994170;