10-97771695-A-G
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Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_003015.3(SFRP5):āc.139T>Cā(p.Tyr47His) variant causes a missense change. The variant allele was found at a frequency of 0.00003 in 1,598,924 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (ā ).
Frequency
Genomes: š 0.000013 ( 0 hom., cov: 32)
Exomes š: 0.000032 ( 0 hom. )
Consequence
SFRP5
NM_003015.3 missense
NM_003015.3 missense
Scores
2
9
8
Clinical Significance
Conservation
PhyloP100: 6.64
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 2 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SFRP5 | NM_003015.3 | c.139T>C | p.Tyr47His | missense_variant | 1/3 | ENST00000266066.4 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SFRP5 | ENST00000266066.4 | c.139T>C | p.Tyr47His | missense_variant | 1/3 | 1 | NM_003015.3 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000131 AC: 2AN: 152094Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.00000886 AC: 2AN: 225826Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 125386
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GnomAD4 exome AF: 0.0000318 AC: 46AN: 1446830Hom.: 0 Cov.: 33 AF XY: 0.0000333 AC XY: 24AN XY: 720304
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GnomAD4 genome ? AF: 0.0000131 AC: 2AN: 152094Hom.: 0 Cov.: 32 AF XY: 0.0000269 AC XY: 2AN XY: 74304
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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 submitter | clinical testing | Ambry Genetics | Jun 30, 2023 | The c.139T>C (p.Y47H) 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 139, causing the tyrosine (Y) at amino acid position 47 to be replaced by a histidine (H). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Pathogenic
DANN
Uncertain
DEOGEN2
Benign
T
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
LIST_S2
Uncertain
D
M_CAP
Pathogenic
D
MetaRNN
Uncertain
D
MetaSVM
Benign
T
MutationAssessor
Uncertain
M
MutationTaster
Benign
D
PrimateAI
Pathogenic
D
PROVEAN
Benign
N
REVEL
Uncertain
Sift
Benign
T
Sift4G
Uncertain
T
Polyphen
D
Vest4
MutPred
Gain of disorder (P = 0.0293);
MVP
MPC
ClinPred
D
GERP RS
Varity_R
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at