1-163168283-G-T

Variant names:

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

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>A​(p.Pro44Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 17/22 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. P44S) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: RGS5 NM_003617.4 missense
• Clinical Significance: Not reported in ClinVar
• 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=0.13353989).

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>A	p.Pro44Thr	missense	Exon 2 of 5	NP_003608.1	O15539-1
	RGS5	NM_001414472.1		c.151C>A	p.Pro51Thr	missense	Exon 4 of 7	NP_001401401.1
	RGS5	NM_001414473.1		c.151C>A	p.Pro51Thr	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>A	p.Pro44Thr	missense	Exon 2 of 5	ENSP00000319308.5	O15539-1
	RGS5	ENST00000527988.1	TSL:1	c.-107-15567C>A		intron	N/A	ENSP00000432313.1	O15539-2
	RGS5	ENST00000367903.7	TSL:3	c.190C>A	p.Pro64Thr	missense	Exon 3 of 6	ENSP00000356879.3	B1APM2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.066
BayesDel_addAF	Benign	-0.14	T
BayesDel_noAF	Benign	-0.44
CADD	Benign	17
DANN	Benign	0.93
DEOGEN2	Benign	0.42	T
Eigen	Benign	-0.19
Eigen_PC	Benign	-0.053
FATHMM_MKL	Benign	0.28	N
LIST_S2	Benign	0.82	T
M_CAP	Benign	0.0086	T
MetaRNN	Benign	0.13	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.1	L
PhyloP100		2.3
PrimateAI	Benign	0.34	T
PROVEAN	Benign	-1.1	N
REVEL	Benign	0.077
Sift	Benign	0.32	T
Sift4G	Benign	0.53	T
Polyphen		0.0020	B
Vest4		0.17
MutPred		0.27		Loss of catalytic residue at P44 (P = 0.0285)
MVP		0.74
MPC		0.20
ClinPred		0.18	T
GERP RS		3.8
Varity_R		0.033
gMVP		0.38
Mutation Taster		=71/29	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; COSMIC: COSV100009116;