1-163152697-TTT-GCG

Variant names:

• chr1-163152697-TTT-GCG
• NM_003617.4:c.235_237delAAAinsCGC
• RGS5 p.Lys79Arg

Variant summary

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

The NM_003617.4(RGS5):​c.235_237delAAAinsCGC​(p.Lys79Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. It is difficult to determine the true allele frequency of this variant because it is of type MNV, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: RGS5 NM_003617.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.26
• 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 Gene-Disease associations (from GenCC):

• essential hypertension, genetic

  Inheritance: Unknown Classification: NO_KNOWN Submitted by: Labcorp Genetics (formerly Invitae)

ACMG classification

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

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.235_237delAAAinsCGC	p.Lys79Arg	missense	N/A	NP_003608.1	O15539-1
	RGS5	NM_001414472.1		c.256_258delAAAinsCGC	p.Lys86Arg	missense	N/A	NP_001401401.1
	RGS5	NM_001414473.1		c.256_258delAAAinsCGC	p.Lys86Arg	missense	N/A	NP_001401402.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RGS5	ENST00000313961.10	TSL:1 MANE Select	c.235_237delAAAinsCGC	p.Lys79Arg	missense	N/A	ENSP00000319308.5	O15539-1
	RGS5	ENST00000527988.1	TSL:1	c.-90_-88delAAAinsCGC		5_prime_UTR	Exon 2 of 3	ENSP00000432313.1	O15539-2
	RGS5	ENST00000367903.7	TSL:3	c.295_297delAAAinsCGC	p.Lys99Arg	missense	N/A	ENSP00000356879.3	B1APM2

Frequencies

GnomAD3 genomes Cov.: 32

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		2.3

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr1-163122487;