Variant chr10-97771527-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_003015.3(SFRP5):c.307G>A(p.Asp103Asn) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00654 in 1,610,364 control chromosomes in the GnomAD database, including 58 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0042 ( 1 hom., cov: 32)

Exomes 𝑓: 0.0068 ( 57 hom. )

Consequence

SFRP5
NM_003015.3 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 7.54

Variant links:

Genes affected

SFRP5 (HGNC:10779): (secreted frizzled related protein 5) Secreted frizzled-related protein 5 (SFRP5) is a member of the SFRP family that contains a cysteine-rich domain homologous to the putative Wnt-binding site of Frizzled proteins. SFRPs act as soluble modulators of Wnt signaling. SFRP5 and SFRP1 may be involved in determining the polarity of photoreceptor cells in the retina. SFRP5 is highly expressed in the retinal pigment epithelium, and moderately expressed in the pancreas. [provided by RefSeq, Jul 2008]

SFRP5 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.011995673).

BP6

Variant 10-97771527-C-T is Benign according to our data. Variant chr10-97771527-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 3387989.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAdExome4 at 57 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SFRP5	NM_003015.3 linkuse as main transcript	c.307G>A	p.Asp103Asn	missense_variant	1/3	ENST00000266066.4	NP_003006.2	Q5T4F7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SFRP5	ENST00000266066.4 linkuse as main transcript	c.307G>A	p.Asp103Asn	missense_variant	1/3	1	NM_003015.3	ENSP00000266066.3		Q5T4F7

Frequencies

GnomAD3 genomes

AF:

0.00418

AC:

636

AN:

152156

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00104

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00393

Gnomad ASJ

AF:

0.000864

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000659

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.00751

Gnomad OTH

AF:

0.00526

GnomAD3 exomes

AF:

0.00395

AC:

967

AN:

244786

Hom.:

AF XY:

0.00386

AC XY:

513

AN XY:

132820

show subpopulations

Gnomad AFR exome

AF:

0.00108

Gnomad AMR exome

AF:

0.00352

Gnomad ASJ exome

AF:

0.00233

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000230

Gnomad FIN exome

AF:

0.000559

Gnomad NFE exome

AF:

0.00689

Gnomad OTH exome

AF:

0.00616

GnomAD4 exome

AF:

0.00679

AC:

9904

AN:

1458090

Hom.:

Cov.:

AF XY:

0.00651

AC XY:

4717

AN XY:

724658

show subpopulations

Gnomad4 AFR exome

AF:

0.00129

Gnomad4 AMR exome

AF:

0.00372

Gnomad4 ASJ exome

AF:

0.00215

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000151

Gnomad4 FIN exome

AF:

0.000827

Gnomad4 NFE exome

AF:

0.00824

Gnomad4 OTH exome

AF:

0.00714

GnomAD4 genome

AF:

0.00417

AC:

635

AN:

152274

Hom.:

Cov.:

AF XY:

0.00352

AC XY:

262

AN XY:

74464

show subpopulations

Gnomad4 AFR

AF:

0.00103

Gnomad4 AMR

AF:

0.00392

Gnomad4 ASJ

AF:

0.000864

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.000659

Gnomad4 NFE

AF:

0.00750

Gnomad4 OTH

AF:

0.00521

Alfa

AF:

0.00684

Hom.:

Bravo

AF:

0.00455

TwinsUK

AF:

0.00324

AC:

ALSPAC

AF:

0.00311

AC:

ESP6500AA

AF:

0.00204

AC:

ESP6500EA

AF:

0.00744

AC:

ExAC

AF:

0.00393

AC:

476

Asia WGS

AF:

0.000577

AC:

AN:

3478

EpiCase

AF:

0.00720

EpiControl

AF:

0.00818

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Oct 01, 2024

SFRP5: BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.59

BayesDel_addAF

Benign

-0.35

BayesDel_noAF

Benign

-0.27

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.28

Eigen

Uncertain

0.56

Eigen_PC

Uncertain

0.53

FATHMM_MKL

Uncertain

0.95

LIST_S2

Uncertain

0.90

M_CAP

Pathogenic

0.67

MetaRNN

Benign

0.012

MetaSVM

Uncertain

-0.18

MutationAssessor

Uncertain

2.3

PrimateAI

Pathogenic

0.82

PROVEAN

Benign

-2.0

REVEL

Uncertain

0.45

Sift

Benign

0.20

Sift4G

Benign

0.30

Polyphen

0.89

Vest4

0.53

MVP

0.77

MPC

1.2

ClinPred

0.023

GERP RS

4.0

Varity_R

0.31

gMVP

0.82

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over