rs545323

Variant names:

• chr6-153024174-C-A
• rs545323
• NM_012419.5:c.444+88G>T

Your query was ambiguous. Multiple possible variants found:

• chr6-153024174-C-A
• chr6-153024174-C-G
• chr6-153024174-C-T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_012419.5(RGS17):​c.444+88G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000306 in 654,652 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000031 (0 hom.)
• Consequence: RGS17 NM_012419.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.921
• Publications: 8 publications found

Genes affected

RGS17 (HGNC:14088): (regulator of G protein signaling 17) This gene encodes a member of the regulator of G-protein signaling family. This protein contains a conserved, 120 amino acid motif called the RGS domain and a cysteine-rich region. The protein attenuates the signaling activity of G-proteins by binding to activated, GTP-bound G alpha subunits and acting as a GTPase activating protein (GAP), increasing the rate of conversion of the GTP to GDP. This hydrolysis allows the G alpha subunits to bind G beta/gamma subunit heterodimers, forming inactive G-protein heterotrimers, thereby terminating the signal. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_012419.5. 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
	RGS17	NM_012419.5	MANE Select	c.444+88G>T		intron	N/A	NP_036551.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RGS17	ENST00000206262.2	TSL:1 MANE Select	c.444+88G>T		intron	N/A	ENSP00000206262.1	Q9UGC6
	RGS17	ENST00000367225.6	TSL:1	c.444+88G>T		intron	N/A	ENSP00000356194.1	Q9UGC6
	RGS17	ENST00000914255.1		c.354+88G>T		intron	N/A	ENSP00000584314.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000306 AC: 2 AN: 654652 Hom.: 0 AF XY: 0.00000290 AC XY: 1 AN XY: 344260

African (AFR) AF: 0.000118 AC: 2 AN: 16956

American (AMR) AF: 0.00 AC: 0 AN: 30038

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 17792

East Asian (EAS) AF: 0.00 AC: 0 AN: 32834

South Asian (SAS) AF: 0.00 AC: 0 AN: 56388

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 43834

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2584

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 421020

Other (OTH) AF: 0.00 AC: 0 AN: 33206

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 10613

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.45
DANN	Benign	0.60
PhyloP100		-0.92

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: rs545323; hg19: chr6-153345309;