rs9491697

Positions:

• chr6-127134977-A-G
• chr6-127134977-A-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_032784.5(RSPO3):​c.98-13671A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.408 in 152,074 control chromosomes in the GnomAD database, including 12,899 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 0.41 (12899 hom., cov: 32)
• Consequence: RSPO3 NM_032784.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.124

Genes affected

RSPO3 (HGNC:20866): (R-spondin 3) This gene belongs to the R-spondin family. The encoded protein plays a role in the regulation of Wnt (wingless-type MMTV integration site family)/beta-catenin and Wnt/planar cell polarity (PCP) signaling pathways, which are involved in development, cell growth and disease pathogenesis. Genome-wide association studies suggest a correlation of this gene with bone mineral density and risk of fracture. This gene may be involved in tumor development. [provided by RefSeq, Jul 2013]

RSPO3 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.516 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RSPO3	NM_032784.5	c.98-13671A>G		intron_variant		ENST00000356698.9	NP_116173.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RSPO3	ENST00000356698.9	c.98-13671A>G		intron_variant		1	NM_032784.5	ENSP00000349131.4

Frequencies

GnomAD3 genomes AF: 0.408 AC: 62050 AN: 151956 Hom.: 12897 Cov.: 32

Gnomad AFR AF: 0.315

Gnomad AMI AF: 0.387

Gnomad AMR AF: 0.413

Gnomad ASJ AF: 0.347

Gnomad EAS AF: 0.533

Gnomad SAS AF: 0.410

Gnomad FIN AF: 0.429

Gnomad MID AF: 0.283

Gnomad NFE AF: 0.456

Gnomad OTH AF: 0.390

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

GnomAD4 genome AF: 0.408 AC: 62075 AN: 152074 Hom.: 12899 Cov.: 32 AF XY: 0.407 AC XY: 30285 AN XY: 74338

Gnomad4 AFR AF: 0.315

Gnomad4 AMR AF: 0.413

Gnomad4 ASJ AF: 0.347

Gnomad4 EAS AF: 0.533

Gnomad4 SAS AF: 0.409

Gnomad4 FIN AF: 0.429

Gnomad4 NFE AF: 0.456

Gnomad4 OTH AF: 0.396

Alfa AF: 0.441 Hom.: 25307

Bravo AF: 0.403

Asia WGS AF: 0.462 AC: 1606 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	2.4
DANN	Benign	0.36

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

Publications

LitVar

Other links and lift over

dbSNP: rs9491697; hg19: chr6-127456122;