dbSNP rs771316827: RGS5:p.Asp99His (chr1-163152639-C-G) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

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

The NM_003617.4(RGS5):c.295G>C(p.Asp99His) variant causes a missense change. The variant allele was found at a frequency of 0.00000548 in 1,460,732 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000055 ( 0 hom. )

Consequence

RGS5
NM_003617.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.88

Publications

0 publications found

Variant links:

Genes affected

RGS5 (HGNC:10001): (regulator of G protein signaling 5) This locus represents naturally occurring readthrough transcription between the neighboring LOC127814295 (uncharacterized LOC127814295) and RGS5 (regulator of G-protein signaling 5) genes on chromosome 1. Some variants of the readthrough transcript encode novel proteins with unique N-termini. [provided by RefSeq, Nov 2022]

RGS5 Gene-Disease associations (from GenCC):

essential hypertension, genetic
Inheritance: Unknown Classification: NO_KNOWN Submitted by: Labcorp Genetics (formerly Invitae)

RGS5 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003617.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
RGS5	NM_003617.4	MANE Select	c.295G>C	p.Asp99His	missense	Exon 4 of 5	NP_003608.1	O15539-1
RGS5	NM_001414472.1		c.316G>C	p.Asp106His	missense	Exon 6 of 7	NP_001401401.1
RGS5	NM_001414473.1		c.316G>C	p.Asp106His	missense	Exon 8 of 9	NP_001401402.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
RGS5	ENST00000313961.10	TSL:1 MANE Select	c.295G>C	p.Asp99His	missense	Exon 4 of 5	ENSP00000319308.5	O15539-1
RGS5	ENST00000527988.1	TSL:1	c.-30G>C		5_prime_UTR	Exon 2 of 3	ENSP00000432313.1	O15539-2
RGS5	ENST00000367903.7	TSL:3	c.355G>C	p.Asp119His	missense	Exon 5 of 6	ENSP00000356879.3	B1APM2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.0000320

AC:

AN:

250234

AF XY:

0.0000370

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000436

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000548

AC:

AN:

1460732

Hom.:

Cov.:

AF XY:

0.00000550

AC XY:

AN XY:

726616

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33440

American (AMR)

AF:

0.00

AC:

AN:

44640

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26110

East Asian (EAS)

AF:

0.000202

AC:

AN:

39670

South Asian (SAS)

AF:

0.00

AC:

AN:

85982

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53404

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5762

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1111368

Other (OTH)

AF:

0.00

AC:

AN:

60356

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.463

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

ExAC

AF:

0.0000165

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.27

BayesDel_addAF

Benign

-0.31

BayesDel_noAF

Benign

-0.36

CADD

Uncertain

(source)

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.44

Eigen

Uncertain

0.46

Eigen_PC

Uncertain

0.46

FATHMM_MKL

Pathogenic

0.97

LIST_S2

Uncertain

0.96

M_CAP

Benign

0.019

MetaRNN

Uncertain

0.47

MetaSVM

Benign

-1.2

MutationAssessor

Pathogenic

3.4

PhyloP100

4.9

PrimateAI

Uncertain

0.51

PROVEAN

Pathogenic

-4.7

REVEL

Benign

0.22

Sift

Uncertain

0.0010

Sift4G

Pathogenic

0.0010

Polyphen

0.44

Vest4

0.49

MutPred

0.62

Gain of MoRF binding (P = 0.0517)

MVP

0.51

MPC

0.73

ClinPred

0.95

GERP RS

4.5

Varity_R

0.66

gMVP

0.58

Mutation Taster

=39/61

disease causing

(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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over