10-86900120-G-C
Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 1P and 0B. PP2
The NM_004329.3(BMPR1A):c.524G>C(p.Cys175Ser) variant causes a missense change. The variant allele was found at a frequency of 0.00000616 in 1,461,144 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. C175Y) has been classified as Uncertain significance.
Frequency
Consequence
NM_004329.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 1 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
BMPR1A | NM_004329.3 | c.524G>C | p.Cys175Ser | missense_variant | 7/13 | ENST00000372037.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
BMPR1A | ENST00000372037.8 | c.524G>C | p.Cys175Ser | missense_variant | 7/13 | 1 | NM_004329.3 | P1 |
Frequencies
GnomAD3 genomes ? Cov.: 33
GnomAD4 exome AF: 0.00000616 AC: 9AN: 1461144Hom.: 0 Cov.: 32 AF XY: 0.00000275 AC XY: 2AN XY: 726928
GnomAD4 genome ? Cov.: 33
ClinVar
Submissions by phenotype
Hereditary cancer-predisposing syndrome Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | May 02, 2022 | The p.C175S variant (also known as c.524G>C), located in coding exon 5 of the BMPR1A gene, results from a G to C substitution at nucleotide position 524. The cysteine at codon 175 is replaced by serine, an amino acid with dissimilar properties. This amino acid position is well conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. - |
Juvenile polyposis syndrome Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Mar 17, 2020 | In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. This variant has not been reported in the literature in individuals with BMPR1A-related disease. ClinVar contains an entry for this variant (Variation ID: 230207). This variant is not present in population databases (ExAC no frequency). This sequence change replaces cysteine with serine at codon 175 of the BMPR1A protein (p.Cys175Ser). The cysteine residue is moderately conserved and there is a moderate physicochemical difference between cysteine and serine. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at