Variant chr6-127119217-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_ModerateBP6_Moderate

The NM_032784.5(RSPO3):c.25C>T(p.Leu9Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,460 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

RSPO3
NM_032784.5 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.80

Variant links:

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 links:

LOC105377989 (HGNC:):

LOC105377989 links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.079698116).

BP6

Variant 6-127119217-C-T is Benign according to our data. Variant chr6-127119217-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 2569510.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RSPO3	NM_032784.5 linkuse as main transcript	c.25C>T	p.Leu9Phe	missense_variant	1/5	ENST00000356698.9	NP_116173.2	Q9BXY4-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RSPO3	ENST00000356698.9 linkuse as main transcript	c.25C>T	p.Leu9Phe	missense_variant	1/5	1	NM_032784.5	ENSP00000349131.4		Q9BXY4-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461460

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

727062

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

9.00e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Apr 07, 2023

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.042

BayesDel_addAF

Benign

-0.14

BayesDel_noAF

Benign

-0.44

CADD

Benign

DANN

Benign

0.93

DEOGEN2

Benign

0.21

T;.

Eigen

Benign

-0.80

Eigen_PC

Benign

-0.65

FATHMM_MKL

Benign

0.19

LIST_S2

Benign

0.31

T;T

M_CAP

Benign

0.022

MetaRNN

Benign

0.080

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.1

L;L

PrimateAI

Uncertain

0.60

PROVEAN

Benign

-0.52

N;N

REVEL

Benign

0.098

Sift

Benign

0.38

T;T

Sift4G

Benign

0.30

T;T

Polyphen

0.0

B;B

Vest4

0.16

MutPred

0.34

Loss of MoRF binding (P = 0.114);Loss of MoRF binding (P = 0.114);

MVP

0.31

MPC

0.55

ClinPred

0.14

GERP RS

1.7

Varity_R

0.040

gMVP

0.40

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

Details are displayed if max score is > 0.2

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

Publications

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over