20-960371-C-A
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_001029871.4(RSPO4):c.691G>T(p.Gly231Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000026 in 1,536,676 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 (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G231S) has been classified as Uncertain significance.
Frequency
Consequence
NM_001029871.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 0 ACMG points.
Transcripts
RefSeq
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
RSPO4 | ENST00000217260.9 | c.691G>T | p.Gly231Cys | missense_variant | Exon 5 of 5 | 1 | NM_001029871.4 | ENSP00000217260.4 | ||
RSPO4 | ENST00000400634.2 | c.505G>T | p.Gly169Cys | missense_variant | Exon 4 of 4 | 1 | ENSP00000383475.2 |
Frequencies
GnomAD3 genomes AF: 0.00000658 AC: 1AN: 152078Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.00000704 AC: 1AN: 141974Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 76164
GnomAD4 exome AF: 0.00000217 AC: 3AN: 1384598Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0AN XY: 683298
GnomAD4 genome AF: 0.00000658 AC: 1AN: 152078Hom.: 0 Cov.: 33 AF XY: 0.0000135 AC XY: 1AN XY: 74268
ClinVar
Submissions by phenotype
Inborn genetic diseases Uncertain:1
The c.691G>T (p.G231C) alteration is located in exon 5 (coding exon 5) of the RSPO4 gene. This alteration results from a G to T substitution at nucleotide position 691, causing the glycine (G) at amino acid position 231 to be replaced by a cysteine (C). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at