chr20-967263-C-T
Variant summary
Our verdict is Likely pathogenic. Variant got 8 ACMG points: 8P and 0B. PM2PM5PP3_Strong
The NM_001029871.4(RSPO4):c.320G>A(p.Cys107Tyr) variant causes a missense change. The variant allele was found at a frequency of 0.00000205 in 1,461,834 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 Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. C107R) has been classified as Pathogenic.
Frequency
Consequence
NM_001029871.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_pathogenic. Variant got 8 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
RSPO4 | NM_001029871.4 | c.320G>A | p.Cys107Tyr | missense_variant | 3/5 | ENST00000217260.9 | |
RSPO4 | NM_001040007.3 | c.320G>A | p.Cys107Tyr | missense_variant | 3/4 | ||
RSPO4 | XM_017027839.2 | c.320G>A | p.Cys107Tyr | missense_variant | 3/4 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
RSPO4 | ENST00000217260.9 | c.320G>A | p.Cys107Tyr | missense_variant | 3/5 | 1 | NM_001029871.4 | P1 | |
RSPO4 | ENST00000400634.2 | c.320G>A | p.Cys107Tyr | missense_variant | 3/4 | 1 |
Frequencies
GnomAD3 genomes ? Cov.: 33
GnomAD4 exome AF: 0.00000205 AC: 3AN: 1461834Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 727222
GnomAD4 genome ? Cov.: 33
ClinVar
Submissions by phenotype
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | Oct 28, 2022 | Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
No publications associated with this variant yet.