Variant 20-64074009-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2

The NM_005873.3(RGS19):c.498C>G(p.Asn166Lys) variant causes a missense change. The variant allele was found at a frequency of 0.0000843 in 1,613,546 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000072 ( 0 hom., cov: 34)

Exomes 𝑓: 0.000086 ( 0 hom. )

Consequence

RGS19
NM_005873.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.83

Variant links:

Genes affected

RGS19 (HGNC:13735): (regulator of G protein signaling 19) G proteins mediate a number of cellular processes. The protein encoded by this gene belongs to the RGS (regulators of G-protein signaling) family and specifically interacts with G protein, GAI3. This protein is a guanosine triphosphatase-activating protein that functions to down-regulate Galpha i/Galpha q-linked signaling. Alternatively spliced transcript variants encoding the same protein isoform have been found for this gene. [provided by RefSeq, Jul 2008]

RGS19 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

BS2

High AC in GnomAd4 at 11 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RGS19	NM_005873.3 link	c.498C>G	p.Asn166Lys	missense_variant	6/6	ENST00000395042.2	NP_005864.1	P49795

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RGS19	ENST00000395042.2 link	c.498C>G	p.Asn166Lys	missense_variant	6/6	1	NM_005873.3	ENSP00000378483.1		P49795
RGS19	ENST00000332298.9 link	c.498C>G	p.Asn166Lys	missense_variant	6/6	1		ENSP00000333194.5		P49795

Frequencies

GnomAD3 genomes

AF:

0.0000723

AC:

AN:

152178

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.000865

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000118

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000153

AC:

AN:

248038

Hom.:

AF XY:

0.000141

AC XY:

AN XY:

134288

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00120

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000235

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000855

AC:

125

AN:

1461368

Hom.:

Cov.:

AF XY:

0.0000935

AC XY:

AN XY:

726970

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.000957

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.0000188

Gnomad4 NFE exome

AF:

0.0000818

Gnomad4 OTH exome

AF:

0.000133

GnomAD4 genome

AF:

0.0000723

AC:

AN:

152178

Hom.:

Cov.:

AF XY:

0.0000404

AC XY:

AN XY:

74340

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.000865

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000118

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000225

Hom.:

Bravo

AF:

0.0000642

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.000115

AC:

EpiCase

AF:

0.000327

EpiControl

AF:

0.000119

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jan 03, 2022

The c.498C>G (p.N166K) alteration is located in exon 6 (coding exon 5) of the RGS19 gene. This alteration results from a C to G substitution at nucleotide position 498, causing the asparagine (N) at amino acid position 166 to be replaced by a lysine (K). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.92

BayesDel_addAF

Benign

-0.37

BayesDel_noAF

Benign

-0.46

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.33

T;T

Eigen

Uncertain

0.38

Eigen_PC

Uncertain

0.39

FATHMM_MKL

Uncertain

0.87

LIST_S2

Uncertain

0.94

D;.

M_CAP

Benign

0.034

MetaRNN

Uncertain

0.57

D;D

MetaSVM

Benign

-0.81

MutationAssessor

Benign

1.4

L;L

PrimateAI

Uncertain

0.63

PROVEAN

Pathogenic

-5.7

D;D

REVEL

Benign

0.23

Sift

Benign

0.20

T;T

Sift4G

Benign

0.12

T;T

Polyphen

1.0

D;D

Vest4

0.72

MutPred

0.35

Loss of ubiquitination at K167 (P = 0.0235);Loss of ubiquitination at K167 (P = 0.0235);

MVP

0.48

MPC

1.5

ClinPred

0.43

GERP RS

4.4

Varity_R

0.54

gMVP

0.54

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

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

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over