5-177367190-G-T

Variant names:

• chr5-177367190-G-T
• rs12654812
• NM_006480.5:c.483+156G>T

Variant summary

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

The NM_006480.5(RGS14):​c.483+156G>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: RGS14 NM_006480.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0770
• Publications: 79 publications found

Genes affected

RGS14 (HGNC:9996): (regulator of G protein signaling 14) This gene encodes a member of the regulator of G-protein signaling family. This protein contains one RGS domain, two Raf-like Ras-binding domains (RBDs), and one GoLoco domain. The protein attenuates the signaling activity of G-proteins by binding, through its GoLoco domain, to specific types of activated, GTP-bound G alpha subunits. Acting as a GTPase activating protein (GAP), the protein increases 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. Alternate transcriptional splice variants of this gene have been observed but have not been thoroughly characterized. [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=-0.79).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RGS14	NM_006480.5	c.483+156G>T		intron_variant	Intron 5 of 14	ENST00000408923.8	NP_006471.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RGS14	ENST00000408923.8	c.483+156G>T		intron_variant	Intron 5 of 14	1	NM_006480.5	ENSP00000386229.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 999624 Hom.: 0 Cov.: 13 AF XY: 0.00 AC XY: 0 AN XY: 497294

African (AFR) AF: 0.00 AC: 0 AN: 23692

American (AMR) AF: 0.00 AC: 0 AN: 21500

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 17222

East Asian (EAS) AF: 0.00 AC: 0 AN: 35970

South Asian (SAS) AF: 0.00 AC: 0 AN: 59898

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 34272

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3004

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 759834

Other (OTH) AF: 0.00 AC: 0 AN: 44232

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	7.6
DANN	Benign	0.92
PhyloP100		-0.077
PromoterAI		-0.076	Neutral

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: rs12654812; hg19: chr5-176794191;