14-72562470-G-C

Variant names:

• chr14-72562470-G-C
• rs2074647
• ENST00000554474.5:n.*141G>C

Variant summary

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

The ENST00000554474.5(RGS6):​n.*141G>C variant causes a non coding transcript exon 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)
• Consequence: RGS6 ENST00000554474.5 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.42
• Publications: 0 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]

ENSG00000258871 (HGNC:):

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=0.26031446).

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000554474.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RGS6	NM_001204424.2	MANE Select	c.*3G>C		3_prime_UTR	Exon 18 of 18	NP_001191353.1
	RGS6	NM_001370275.1		c.1543G>C	p.Val515Leu	missense	Exon 19 of 20	NP_001357204.1
	RGS6	NM_001370276.1		c.1543G>C	p.Val515Leu	missense	Exon 19 of 20	NP_001357205.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RGS6	ENST00000554474.5	TSL:1	n.*141G>C		non_coding_transcript_exon	Exon 19 of 19	ENSP00000450858.1
	RGS6	ENST00000553525.6	TSL:2 MANE Select	c.*3G>C		3_prime_UTR	Exon 18 of 18	ENSP00000451030.1
	RGS6	ENST00000556437.5	TSL:1	c.*3G>C		3_prime_UTR	Exon 18 of 18	ENSP00000451855.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.17
BayesDel_noAF	Benign	-0.66
CADD	Benign	15
DANN	Benign	0.84
FATHMM_MKL	Benign	0.51	D
LIST_S2	Benign	0.31	T
MetaRNN	Benign	0.26	T
PhyloP100		3.4
GERP RS		3.4
Mutation Taster		=100/0	polymorphism

Splicing

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

Other links and lift over

dbSNP: rs2074647; hg19: chr14-73029178;