rs759477959

Variant names:

• chr1-163168283-G-A
• rs759477959
• NM_003617.4:c.130C>T

Your query was ambiguous. Multiple possible variants found:

• chr1-163168283-G-A
• chr1-163168283-G-C
• chr1-163168283-G-T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_003617.4(RGS5):​c.130C>T​(p.Pro44Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000205 in 1,461,424 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.000021 (0 hom.)
• Consequence: RGS5 NM_003617.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.33
• Publications: 0 publications found

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-AS1 (HGNC:40504): (RGS5 antisense RNA 1)

ACMG classification

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

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.11994994).

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RGS5	NM_003617.4	MANE Select	c.130C>T	p.Pro44Ser	missense	Exon 2 of 5	NP_003608.1	O15539-1
	RGS5	NM_001414472.1		c.151C>T	p.Pro51Ser	missense	Exon 4 of 7	NP_001401401.1
	RGS5	NM_001414473.1		c.151C>T	p.Pro51Ser	missense	Exon 6 of 9	NP_001401402.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RGS5	ENST00000313961.10	TSL:1 MANE Select	c.130C>T	p.Pro44Ser	missense	Exon 2 of 5	ENSP00000319308.5	O15539-1
	RGS5	ENST00000527988.1	TSL:1	c.-107-15567C>T		intron	N/A	ENSP00000432313.1	O15539-2
	RGS5	ENST00000367903.7	TSL:3	c.190C>T	p.Pro64Ser	missense	Exon 3 of 6	ENSP00000356879.3	B1APM2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000796 AC: 2 AN: 251248 AF XY: 0.00000736

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 FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000176

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000205 AC: 30 AN: 1461424 Hom.: 0 Cov.: 30 AF XY: 0.0000193 AC XY: 14 AN XY: 727034

African (AFR) AF: 0.00 AC: 0 AN: 33460

American (AMR) AF: 0.00 AC: 0 AN: 44712

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26124

East Asian (EAS) AF: 0.00 AC: 0 AN: 39686

South Asian (SAS) AF: 0.00 AC: 0 AN: 86240

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53414

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5766

European-Non Finnish (NFE) AF: 0.0000270 AC: 30 AN: 1111644

Other (OTH) AF: 0.00 AC: 0 AN: 60378

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.085
BayesDel_addAF	Benign	-0.14	T
BayesDel_noAF	Benign	-0.42
CADD	Benign	17
DANN	Uncertain	1.0
DEOGEN2	Benign	0.41	T
Eigen	Benign	-0.17
Eigen_PC	Benign	-0.045
FATHMM_MKL	Benign	0.28	N
LIST_S2	Benign	0.84	T
M_CAP	Benign	0.0088	T
MetaRNN	Benign	0.12	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.4	L
PhyloP100		2.3
PrimateAI	Benign	0.32	T
PROVEAN	Benign	-1.3	N
REVEL	Benign	0.094
Sift	Benign	0.60	T
Sift4G	Benign	0.79	T
Polyphen		0.0060	B
Vest4		0.15
MutPred		0.29		Loss of catalytic residue at P44 (P = 0.0168)
MVP		0.76
MPC		0.18
ClinPred		0.16	T
GERP RS		3.8
Varity_R		0.024
gMVP		0.36
Mutation Taster		=77/23	polymorphism

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

Other links and lift over

dbSNP: rs759477959; hg19: chr1-163138073;