rs755007671
Positions:
Variant summary
Our verdict is Pathogenic. Variant got 11 ACMG points: 11P and 0B. PVS1PM2PP5
The NM_003014.4(SFRP4):c.694C>T(p.Arg232Ter) variant causes a stop gained change. The variant allele was found at a frequency of 0.00000684 in 1,461,796 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Pathogenic (no stars). Variant results in nonsense mediated mRNA decay.
Frequency
Genomes: not found (cov: 32)
Exomes 𝑓: 0.0000068 ( 0 hom. )
Consequence
SFRP4
NM_003014.4 stop_gained
NM_003014.4 stop_gained
Scores
4
2
1
Clinical Significance
Conservation
PhyloP100: 3.81
Genes affected
SFRP4 (HGNC:10778): (secreted frizzled related protein 4) Secreted frizzled-related protein 4 (SFRP4) 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. The expression of SFRP4 in ventricular myocardium correlates with apoptosis related gene expression. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Pathogenic. Variant got 11 ACMG points.
PVS1
?
Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
PM2
?
Very rare variant in population databases, with high coverage;
PP5
?
Variant 7-37912216-G-A is Pathogenic according to our data. Variant chr7-37912216-G-A is described in ClinVar as [Pathogenic]. Clinvar id is 242996.Status of the report is no_assertion_criteria_provided, 0 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SFRP4 | NM_003014.4 | c.694C>T | p.Arg232Ter | stop_gained | 4/6 | ENST00000436072.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SFRP4 | ENST00000436072.7 | c.694C>T | p.Arg232Ter | stop_gained | 4/6 | 1 | NM_003014.4 | P1 | |
SFRP4 | ENST00000447200.2 | c.292C>T | p.Arg98Ter | stop_gained | 5/6 | 5 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD3 genomes
?
Cov.:
32
GnomAD3 exomes AF: 0.00000398 AC: 1AN: 251482Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 135918
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GnomAD4 exome AF: 0.00000684 AC: 10AN: 1461796Hom.: 0 Cov.: 33 AF XY: 0.0000110 AC XY: 8AN XY: 727208
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GnomAD4 genome ? Cov.: 32
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ClinVar
Significance: Pathogenic
Submissions summary: Pathogenic:1
Revision: no assertion criteria provided
LINK: link
Submissions by phenotype
Pyle metaphyseal dysplasia Pathogenic:1
Pathogenic, no assertion criteria provided | literature only | OMIM | Oct 03, 2017 | - - |
Computational scores
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Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
CADD
Pathogenic
DANN
Uncertain
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Uncertain
D
MutationTaster
Benign
D;A
Vest4
GERP RS
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