14-72472787-C-T

Variant names:

• chr14-72472787-C-T
• rs10131300
• NM_001204424.2:c.537-85C>T

Variant summary

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

The NM_001204424.2(RGS6):​c.537-85C>T variant causes a intron 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: RGS6 NM_001204424.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.144
• Publications: 12 publications found

Genes affected

RGS6 (HGNC:10002): (regulator of G protein signaling 6) This gene encodes a member of the RGS (regulator of G protein signaling) family of proteins, which are defined by the presence of a RGS domain that confers the GTPase-activating activity of these proteins toward certain G alpha subunits. This protein also belongs to a subfamily of RGS proteins characterized by the presence of DEP and GGL domains, the latter a G beta 5-interacting domain. The RGS proteins negatively regulate G protein signaling, and may modulate neuronal, cardiovascular, lymphocytic activities, and cancer risk. Many alternatively spliced transcript variants encoding different isoforms with long or short N-terminal domains, complete or incomplete GGL domains, and distinct C-terminal domains, have been described for this gene, however, the full-length nature of some of these variants is not known.[provided by RefSeq, Mar 2011]

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=-0.78).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RGS6	NM_001204424.2	c.537-85C>T		intron_variant	Intron 8 of 17	ENST00000553525.6	NP_001191353.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RGS6	ENST00000553525.6	c.537-85C>T		intron_variant	Intron 8 of 17	2	NM_001204424.2	ENSP00000451030.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0;AS_VQSR AF: 0.00 AC: 0 AN: 829914 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 434018

African (AFR) AF: 0.00 AC: 0 AN: 19606

American (AMR) AF: 0.00 AC: 0 AN: 34182

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 18358

East Asian (EAS) AF: 0.00 AC: 0 AN: 35074

South Asian (SAS) AF: 0.00 AC: 0 AN: 62888

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 49386

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4316

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 567662

Other (OTH) AF: 0.00 AC: 0 AN: 38442

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 150624

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	3.0
DANN	Benign	0.87
PhyloP100		-0.14

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: rs10131300; hg19: chr14-72939495;