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GeneBe

8-99962441-A-G

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 2P and 10B. PM2BP4_StrongBP6_ModerateBS2

The NM_015668.5(RGS22):c.3793T>C(p.Ter1265ArgextTer34) variant causes a stop lost, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00025 in 1,613,622 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.00045 ( 0 hom., cov: 32)
Exomes 𝑓: 0.00023 ( 1 hom. )

Consequence

RGS22
NM_015668.5 stop_lost, splice_region

Scores

1
6

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.96
Variant links:
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]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

PM2
?
    PM2 - Absent from controls (or at extremely low frequency if recessive) in Exome Sequencing Project, 1000 Genomes Project, or Exome Aggregation Consortium
Very rare variant in population databases, with high coverage;
BP4
?
    BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (BayesDel_addAF=-0.534168).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 8-99962441-A-G is Benign according to our data. Variant chr8-99962441-A-G is described in ClinVar as [Benign]. Clinvar id is 716535.Status of the report is criteria_provided_single_submitter, 1 stars.
BS2
?
    BS2 - Observed in a healthy adult individual for a recessive (homozygous), dominant (heterozygous), or X-linked (hemizygous) disorder, with full penetrance expected at an early age
High Homozygotes in GnomAdExome at 2 AR gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
RGS22NM_015668.5 linkuse as main transcriptc.3793T>C p.Ter1265ArgextTer34 stop_lost, splice_region_variant 27/28 ENST00000360863.11

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
RGS22ENST00000360863.11 linkuse as main transcriptc.3793T>C p.Ter1265ArgextTer34 stop_lost, splice_region_variant 27/281 NM_015668.5 P3Q8NE09-1

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.000447
AC:
68
AN:
152194
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000524
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.0111
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.000957
GnomAD3 exomes
AF:
0.000812
AC:
202
AN:
248880
Hom.:
2
AF XY:
0.000763
AC XY:
103
AN XY:
135004
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.0000290
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.0110
Gnomad SAS exome
AF:
0.0000327
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.000331
GnomAD4 exome
AF:
0.000229
AC:
335
AN:
1461310
Hom.:
1
Cov.:
29
AF XY:
0.000206
AC XY:
150
AN XY:
727000
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.0000224
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00708
Gnomad4 SAS exome
AF:
0.0000116
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000360
Gnomad4 OTH exome
AF:
0.000795
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.000453
AC:
69
AN:
152312
Hom.:
0
Cov.:
32
AF XY:
0.000376
AC XY:
28
AN XY:
74490
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.000523
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.0112
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00142
Alfa
AF:
0.000393
Hom.:
1
Bravo
AF:
0.000427
ExAC
?
    Exome Aggregation Consortium database
AF:
0.000761
AC:
92
Asia WGS
AF:
0.00260
AC:
9
AN:
3478

ClinVar

Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Benign:1
Benign, criteria provided, single submitterclinical testingInvitaeMar 30, 2018- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Benign
-0.53
T
BayesDel_noAF
Benign
-0.53
Cadd
Benign
15
Dann
Benign
0.78
Eigen
Uncertain
0.50
Eigen_PC
Benign
0.20
FATHMM_MKL
Benign
0.45
N
MutationTaster
Benign
1.0
N;N;N
Vest4
0.030
GERP RS
2.8

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.050
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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs139157188; hg19: chr8-100974669; API