chr20-960382-G-T
Variant summary
Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2
The NM_001029871.4(RSPO4):c.680C>A(p.Pro227Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000397 in 1,537,808 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Synonymous variant affecting the same amino acid position (i.e. P227P) has been classified as Likely benign.
Frequency
Consequence
NM_001029871.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -8 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
RSPO4 | NM_001029871.4 | c.680C>A | p.Pro227Gln | missense_variant | 5/5 | ENST00000217260.9 | |
RSPO4 | NM_001040007.3 | c.494C>A | p.Pro165Gln | missense_variant | 4/4 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
RSPO4 | ENST00000217260.9 | c.680C>A | p.Pro227Gln | missense_variant | 5/5 | 1 | NM_001029871.4 | P1 | |
RSPO4 | ENST00000400634.2 | c.494C>A | p.Pro165Gln | missense_variant | 4/4 | 1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000131 AC: 2AN: 152154Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.000160 AC: 23AN: 143320Hom.: 2 AF XY: 0.000260 AC XY: 20AN XY: 76826
GnomAD4 exome AF: 0.0000426 AC: 59AN: 1385536Hom.: 2 Cov.: 31 AF XY: 0.0000643 AC XY: 44AN XY: 683824
GnomAD4 genome ? AF: 0.0000131 AC: 2AN: 152272Hom.: 0 Cov.: 33 AF XY: 0.0000134 AC XY: 1AN XY: 74442
ClinVar
Submissions by phenotype
Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Feb 21, 2024 | The c.680C>A (p.P227Q) alteration is located in exon 5 (coding exon 5) of the RSPO4 gene. This alteration results from a C to A substitution at nucleotide position 680, causing the proline (P) at amino acid position 227 to be replaced by a glutamine (Q). 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