Genetic Variant ENST00000392865.5:c.-47C>T (chr10-119536517-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The ENST00000392865.5(RGS10):c.-47C>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0768 in 1,607,164 control chromosomes in the GnomAD database, including 5,368 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.062 ( 395 hom., cov: 32)

Exomes 𝑓: 0.078 ( 4973 hom. )

Consequence

RGS10
ENST00000392865.5 5_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.41

Publications

12 publications found

Variant links:

Genes affected

RGS10 (HGNC:9992): (regulator of G protein signaling 10) 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 10 belongs to this family. All RGS proteins share a conserved 120-amino acid sequence termed the RGS domain. This protein associates specifically with the activated forms of the two related G-protein subunits, G-alphai3 and G-alphaz but fails to interact with the structurally and functionally distinct G-alpha subunits. Regulator of G protein signaling 10 protein is localized in the nucleus. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

RGS10 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.6).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0862 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RGS10	NM_001005339.2 link	c.49+6073C>T		intron_variant	Intron 1 of 4	ENST00000369103.3	NP_001005339.1	O43665-3
RGS10	NM_002925.4 link	c.-47C>T		5_prime_UTR_variant	Exon 1 of 5		NP_002916.1	O43665-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RGS10	ENST00000392865.5 link	c.-47C>T		5_prime_UTR_variant	Exon 1 of 5	1		ENSP00000376605.1		O43665-2
RGS10	ENST00000369103.3 link	c.49+6073C>T		intron_variant	Intron 1 of 4	1	NM_001005339.2	ENSP00000358099.2		O43665-3

Frequencies

GnomAD3 genomes

AF:

0.0617

AC:

9393

AN:

152124

Hom.:

395

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0286

Gnomad AMI

AF:

0.0647

Gnomad AMR

AF:

0.0826

Gnomad ASJ

AF:

0.0675

Gnomad EAS

AF:

0.000577

Gnomad SAS

AF:

0.0234

Gnomad FIN

AF:

0.0348

Gnomad MID

AF:

0.0696

Gnomad NFE

AF:

0.0881

Gnomad OTH

AF:

0.0757

GnomAD2 exomes

AF:

0.0612

AC:

14532

AN:

237564

AF XY:

0.0620

show subpopulations

Gnomad AFR exome

AF:

0.0307

Gnomad AMR exome

AF:

0.0572

Gnomad ASJ exome

AF:

0.0717

Gnomad EAS exome

AF:

0.000403

Gnomad FIN exome

AF:

0.0333

Gnomad NFE exome

AF:

0.0889

Gnomad OTH exome

AF:

0.0816

GnomAD4 exome

AF:

0.0783

AC:

113978

AN:

1454922

Hom.:

4973

Cov.:

AF XY:

0.0774

AC XY:

56002

AN XY:

723280

show subpopulations

African (AFR)

AF:

0.0307

AC:

1021

AN:

33298

American (AMR)

AF:

0.0603

AC:

2651

AN:

43970

Ashkenazi Jewish (ASJ)

AF:

0.0718

AC:

1866

AN:

25978

East Asian (EAS)

AF:

0.000279

AC:

AN:

39412

South Asian (SAS)

AF:

0.0287

AC:

2435

AN:

84960

European-Finnish (FIN)

AF:

0.0366

AC:

1941

AN:

53062

Middle Eastern (MID)

AF:

0.0986

AC:

568

AN:

5758

European-Non Finnish (NFE)

AF:

0.0892

AC:

98887

AN:

1108344

Other (OTH)

AF:

0.0765

AC:

4598

AN:

60140

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.458

Heterozygous variant carriers

4602

9204

13807

18409

23011

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0617

AC:

9393

AN:

152242

Hom.:

395

Cov.:

AF XY:

0.0587

AC XY:

4368

AN XY:

74440

show subpopulations

African (AFR)

AF:

0.0285

AC:

1185

AN:

41548

American (AMR)

AF:

0.0824

AC:

1260

AN:

15294

Ashkenazi Jewish (ASJ)

AF:

0.0675

AC:

234

AN:

3468

East Asian (EAS)

AF:

0.000578

AC:

AN:

5188

South Asian (SAS)

AF:

0.0234

AC:

113

AN:

4826

European-Finnish (FIN)

AF:

0.0348

AC:

369

AN:

10600

Middle Eastern (MID)

AF:

0.0748

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0881

AC:

5991

AN:

68002

Other (OTH)

AF:

0.0744

AC:

157

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.497

Heterozygous variant carriers

448

896

1343

1791

2239

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.0847

Hom.:

961

Bravo

AF:

0.0654

Asia WGS

AF:

0.0200

AC:

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.60

CADD

Benign

(source)

DANN

Benign

0.82

PhyloP100

1.4

PromoterAI

-0.043

Neutral

(source)

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

ENST00000392865.5:c.-47C>T

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over