rs200637581

Variant names:

• chr20-64074527-C-A
• NM_005873.3:c.167G>T

Your query was ambiguous. Multiple possible variants found:

• chr20-64074527-C-A
• chr20-64074527-C-T

Variant summary

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

The NM_005873.3(RGS19):​c.167G>T​(p.Arg56Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000709 in 1,410,638 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R56Q) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 34)
  • Exomes 𝑓: 7.1e-7 (0 hom.)
• Consequence: RGS19 NM_005873.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.729

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=0.13220799).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RGS19	NM_005873.3	c.167G>T	p.Arg56Leu	missense_variant	Exon 4 of 6	ENST00000395042.2	NP_005864.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RGS19	ENST00000395042.2	c.167G>T	p.Arg56Leu	missense_variant	Exon 4 of 6	1	NM_005873.3	ENSP00000378483.1
RGS19	ENST00000332298.9	c.167G>T	p.Arg56Leu	missense_variant	Exon 4 of 6	1		ENSP00000333194.5
RGS19	ENST00000493165.1	n.753G>T		non_coding_transcript_exon_variant	Exon 4 of 4	3

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome AF: 7.09e-7 AC: 1 AN: 1410638 Hom.: 0 Cov.: 34 AF XY: 0.00 AC XY: 0 AN XY: 697210

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000272

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 34

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.072	T
BayesDel_noAF	Benign	-0.34
CADD	Benign	20
DANN	Uncertain	0.98
DEOGEN2	Benign	0.32	T;T
Eigen	Benign	-0.59
Eigen_PC	Benign	-0.51
FATHMM_MKL	Benign	0.19	N
LIST_S2	Benign	0.75	T;.
M_CAP	Benign	0.059	D
MetaRNN	Benign	0.13	T;T
MetaSVM	Benign	-0.89	T
MutationAssessor	Benign	1.8	L;L
PrimateAI	Benign	0.45	T
PROVEAN	Benign	-1.8	N;N
REVEL	Benign	0.11
Sift	Uncertain	0.0080	D;D
Sift4G	Benign	0.19	T;T
Polyphen		0.081	B;B
Vest4		0.40
MutPred		0.23		Loss of MoRF binding (P = 0.0232);Loss of MoRF binding (P = 0.0232);
MVP		0.51
MPC		0.76
ClinPred		0.23	T
GERP RS		2.7
Varity_R		0.082
gMVP		0.50

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: chr20-62705880;