10-119522095-A-G

Variant names:

• chr10-119522095-A-G
• rs1467813
• NM_001005339.2:c.255+3937T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001005339.2(RGS10):​c.255+3937T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.711 in 152,116 control chromosomes in the GnomAD database, including 38,565 homozygotes. 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: 𝑓 0.71 (38565 hom., cov: 32)
• Consequence: RGS10 NM_001005339.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.899
• Publications: 3 publications found

Genes affected

RGS10 (HGNC:9992): (regulator of G protein signaling 10) Regulator of G protein signaling (RGS) family members are regulatory molecules that act as GTPase activating proteins (GAPs) for G alpha subunits of heterotrimeric G proteins. RGS proteins are able to deactivate G protein subunits of the Gi alpha, Go alpha and Gq alpha subtypes. They drive G proteins into their inactive GDP-bound forms. Regulator of G protein signaling 10 belongs to this family. All RGS proteins share a conserved 120-amino acid sequence termed the RGS domain. This protein associates specifically with the activated forms of the two related G-protein subunits, G-alphai3 and G-alphaz but fails to interact with the structurally and functionally distinct G-alpha subunits. Regulator of G protein signaling 10 protein is localized in the nucleus. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.763 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RGS10	NM_001005339.2	c.255+3937T>C		intron_variant	Intron 3 of 4	ENST00000369103.3	NP_001005339.1
RGS10	NM_002925.4	c.213+3937T>C		intron_variant	Intron 3 of 4		NP_002916.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RGS10	ENST00000369103.3	c.255+3937T>C		intron_variant	Intron 3 of 4	1	NM_001005339.2	ENSP00000358099.2
RGS10	ENST00000369101.7	c.231+3937T>C		intron_variant	Intron 2 of 3	1		ENSP00000358097.3
RGS10	ENST00000392865.5	c.213+3937T>C		intron_variant	Intron 3 of 4	1		ENSP00000376605.1
RGS10	ENST00000469575.1	n.63+3937T>C		intron_variant	Intron 1 of 2	3

Frequencies

GnomAD3 genomes AF: 0.711 AC: 108108 AN: 151998 Hom.: 38532 Cov.: 32

Gnomad AFR AF: 0.689

Gnomad AMI AF: 0.764

Gnomad AMR AF: 0.752

Gnomad ASJ AF: 0.649

Gnomad EAS AF: 0.734

Gnomad SAS AF: 0.784

Gnomad FIN AF: 0.698

Gnomad MID AF: 0.671

Gnomad NFE AF: 0.714

Gnomad OTH AF: 0.698

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

GnomAD4 genome AF: 0.711 AC: 108197 AN: 152116 Hom.: 38565 Cov.: 32 AF XY: 0.713 AC XY: 53013 AN XY: 74350

African (AFR) AF: 0.689 AC: 28577 AN: 41484

American (AMR) AF: 0.752 AC: 11492 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.649 AC: 2253 AN: 3472

East Asian (EAS) AF: 0.734 AC: 3796 AN: 5170

South Asian (SAS) AF: 0.784 AC: 3782 AN: 4824

European-Finnish (FIN) AF: 0.698 AC: 7376 AN: 10572

Middle Eastern (MID) AF: 0.667 AC: 196 AN: 294

European-Non Finnish (NFE) AF: 0.714 AC: 48548 AN: 67996

Other (OTH) AF: 0.701 AC: 1480 AN: 2110

Alfa AF: 0.712 Hom.: 63499

Bravo AF: 0.713

Asia WGS AF: 0.781 AC: 2711 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.47
DANN	Benign	0.58
PhyloP100		-0.90
Mutation Taster		=100/0	polymorphism (auto)

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: rs1467813; hg19: chr10-121281607;