chr6-127195877-A-C

Variant names:

• chr6-127195877-A-C
• NM_032784.5:c.689A>C

Variant summary

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

The NM_032784.5(RSPO3):​c.689A>C​(p.Glu230Ala) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: RSPO3 NM_032784.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.74
• Publications: 0 publications found

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]

ENSG00000293110 (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=0.1399315).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_032784.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RSPO3	NM_032784.5	MANE Select	c.689A>C	p.Glu230Ala	missense	Exon 5 of 5	NP_116173.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RSPO3	ENST00000356698.9	TSL:1 MANE Select	c.689A>C	p.Glu230Ala	missense	Exon 5 of 5	ENSP00000349131.4	Q9BXY4-1
	RSPO3	ENST00000368317.3	TSL:2	c.689A>C	p.Glu230Ala	missense	Exon 5 of 6	ENSP00000357300.3	Q9BXY4-2
	RSPO3	ENST00000858748.1		c.497A>C	p.Glu166Ala	missense	Exon 4 of 4	ENSP00000528807.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Benign	-0.017	T
BayesDel_noAF	Benign	-0.26
CADD	Benign	23
DANN	Uncertain	0.99
DEOGEN2	Benign	0.27	T
Eigen	Benign	0.088
Eigen_PC	Uncertain	0.26
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Benign	0.76	T
M_CAP	Benign	0.051	D
MetaRNN	Benign	0.14	T
MetaSVM	Benign	-0.63	T
MutationAssessor	Benign	0.69	N
PhyloP100		5.7
PrimateAI	Benign	0.38	T
PROVEAN	Benign	-2.1	N
REVEL	Benign	0.25
Sift	Uncertain	0.0060	D
Sift4G	Benign	0.21	T
Polyphen		0.083	B
Vest4		0.12
MutPred		0.17		Gain of MoRF binding (P = 0.0267)
MVP		0.74
MPC		0.59
ClinPred		0.70	D
GERP RS		5.7
Varity_R		0.13
gMVP		0.31
Mutation Taster		=77/23	polymorphism

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

hg19: chr6-127517022;