20-64073999-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_005873.3(RGS19):c.508C>G(p.Gln170Glu) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 34)
• Consequence: RGS19 NM_005873.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.63

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.16675043).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RGS19	NM_005873.3	c.508C>G	p.Gln170Glu	missense_variant	6/6	ENST00000395042.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RGS19	ENST00000395042.2	c.508C>G	p.Gln170Glu	missense_variant	6/6	1	NM_005873.3	P1
RGS19	ENST00000332298.9	c.508C>G	p.Gln170Glu	missense_variant	6/6	1		P1

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 34

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Mar 29, 2023

The c.508C>G (p.Q170E) 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 508, causing the glutamine (Q) at amino acid position 170 to be replaced by a glutamic acid (E). 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	0.088
BayesDel_addAF	Benign	-0.18	T
BayesDel_noAF	Benign	-0.49
Cadd	Benign	23
Dann	Benign	0.84
DEOGEN2	Benign	0.23	T;T
Eigen	Benign	-0.074
Eigen_PC	Benign	0.13
FATHMM_MKL	Uncertain	0.91	D
LIST_S2	Benign	0.84	T;.
M_CAP	Benign	0.021	T
MetaRNN	Benign	0.17	T;T
MetaSVM	Benign	-0.77	T
MutationAssessor	Benign	0.84	L;L
MutationTaster	Benign	1.0	D;D
PrimateAI	Uncertain	0.52	T
PROVEAN	Benign	-1.1	N;N
REVEL	Benign	0.21
Sift	Benign	0.96	T;T
Sift4G	Benign	1.0	T;T
Polyphen		0.027	B;B
Vest4		0.31
MutPred		0.37		Gain of ubiquitination at K168 (P = 0.0731);Gain of ubiquitination at K168 (P = 0.0731);
MVP		0.26
MPC		0.81
ClinPred		0.49	T
GERP RS		5.5
Varity_R		0.31
gMVP		0.36

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr20-62705352;