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GeneBe

10-97771769-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_003015.3(SFRP5):c.65T>C(p.Leu22Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000131 in 1,524,616 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)
Exomes 𝑓: 7.3e-7 ( 0 hom. )

Consequence

SFRP5
NM_003015.3 missense

Scores

2
1
16

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.545
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]

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.18343002).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
SFRP5NM_003015.3 linkuse as main transcriptc.65T>C p.Leu22Pro missense_variant 1/3 ENST00000266066.4

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
SFRP5ENST00000266066.4 linkuse as main transcriptc.65T>C p.Leu22Pro missense_variant 1/31 NM_003015.3 P1

Frequencies

GnomAD3 genomes
AF:
0.00000663
AC:
1
AN:
150780
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.000195
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.00
GnomAD4 exome
AF:
7.28e-7
AC:
1
AN:
1373726
Hom.:
0
Cov.:
33
AF XY:
0.00
AC XY:
0
AN XY:
682358
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0000303
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.00000663
AC:
1
AN:
150890
Hom.:
0
Cov.:
32
AF XY:
0.00
AC XY:
0
AN XY:
73718
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.000195
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingAmbry GeneticsMar 20, 2023The c.65T>C (p.L22P) alteration is located in exon 1 (coding exon 1) of the SFRP5 gene. This alteration results from a T to C substitution at nucleotide position 65, causing the leucine (L) at amino acid position 22 to be replaced by a proline (P). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.10
BayesDel_addAF
Benign
-0.070
T
BayesDel_noAF
Benign
-0.34
Cadd
Benign
23
Dann
Benign
0.96
DEOGEN2
Benign
0.17
T
Eigen
Benign
-0.65
Eigen_PC
Benign
-0.59
FATHMM_MKL
Benign
0.013
N
LIST_S2
Benign
0.37
T
M_CAP
Pathogenic
0.45
D
MetaRNN
Benign
0.18
T
MetaSVM
Benign
-0.99
T
MutationAssessor
Benign
0.69
N
MutationTaster
Benign
1.0
N
PrimateAI
Pathogenic
0.92
D
PROVEAN
Benign
-0.69
N
REVEL
Benign
0.16
Sift
Benign
0.13
T
Sift4G
Uncertain
0.056
T
Polyphen
0.0
B
Vest4
0.22
MutPred
0.64
Gain of loop (P = 0.0013);
MVP
0.61
MPC
0.82
ClinPred
0.082
T
GERP RS
2.5
Varity_R
0.29
gMVP
0.65

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr10-99531526; API