Variant chr20-64076859-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP4BS2

The NM_005873.3(RGS19):c.28C>A(p.Gln10Lys) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000638 in 1,411,138 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/23 in silico tools predict a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000064 ( 0 hom. )

Consequence

RGS19
NM_005873.3 missense, splice_region

Scores

Splicing: ADA: 0.4479

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.65

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:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -5 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.27365416).

BS2

High AC in GnomAdExome4 at 9 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RGS19	NM_005873.3 link	c.28C>A	p.Gln10Lys	missense_variant, splice_region_variant	2/6	ENST00000395042.2	NP_005864.1	P49795

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
RGS19	ENST00000395042.2 link	c.28C>A	p.Gln10Lys	missense_variant, splice_region_variant	2/6	1	NM_005873.3	ENSP00000378483.1	P49795
RGS19	ENST00000332298.9 link	c.28C>A	p.Gln10Lys	missense_variant, splice_region_variant	2/6	1		ENSP00000333194.5	P49795
RGS19	ENST00000493165.1 link	n.614C>A		splice_region_variant, non_coding_transcript_exon_variant	2/4	3
RGS19	ENST00000479996.1 link	n.133-213C>A		intron_variant		2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000259

AC:

AN:

193068

Hom.:

AF XY:

0.0000470

AC XY:

AN XY:

106288

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000545

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000638

AC:

AN:

1411138

Hom.:

Cov.:

AF XY:

0.00000713

AC XY:

AN XY:

700888

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000731

Gnomad4 OTH exome

AF:

0.0000172

GnomAD4 genome

Cov.:

ExAC

AF:

0.0000248

AC:

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

Nov 18, 2023

The c.28C>A (p.Q10K) alteration is located in exon 2 (coding exon 1) of the RGS19 gene. This alteration results from a C to A substitution at nucleotide position 28, causing the glutamine (Q) at amino acid position 10 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

Benign

0.085

BayesDel_addAF

Benign

-0.098

BayesDel_noAF

Benign

-0.22

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.26

T;T

Eigen

Benign

0.094

Eigen_PC

Benign

0.13

FATHMM_MKL

Uncertain

0.76

LIST_S2

Benign

0.70

T;.

M_CAP

Uncertain

0.10

MetaRNN

Benign

0.27

T;T

MetaSVM

Benign

-0.72

MutationAssessor

Uncertain

2.1

M;M

PrimateAI

Uncertain

0.74

PROVEAN

Benign

-0.45

N;N

REVEL

Benign

0.27

Sift

Uncertain

0.027

D;D

Sift4G

Benign

0.22

T;T

Polyphen

0.93

P;P

Vest4

0.49

MutPred

0.16

Gain of ubiquitination at Q10 (P = 0.001);Gain of ubiquitination at Q10 (P = 0.001);

MVP

0.78

MPC

1.5

ClinPred

0.30

GERP RS

3.6

Varity_R

0.096

gMVP

0.31

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.45

dbscSNV1_RF

Benign

0.54

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