chr7-151176251-G-C
Variant summary
Our verdict is Likely benign. Variant got -3 ACMG points: 1P and 4B. PP3BS2
The NM_001142459.2(ASB10):c.1265C>G(p.Pro422Arg) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000107 in 1,587,528 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. P422H) has been classified as Uncertain significance.
Frequency
Consequence
NM_001142459.2 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -3 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ASB10 | NM_001142459.2 | c.1265C>G | p.Pro422Arg | missense_variant | 5/6 | ENST00000420175.3 | |
ASB10 | NM_080871.4 | c.1220C>G | p.Pro407Arg | missense_variant | 5/6 | ||
ASB10 | NM_001142460.1 | c.1151C>G | p.Pro384Arg | missense_variant | 4/5 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ASB10 | ENST00000420175.3 | c.1265C>G | p.Pro422Arg | missense_variant | 5/6 | 1 | NM_001142459.2 | P4 | |
ASB10 | ENST00000275838.5 | c.1151C>G | p.Pro384Arg | missense_variant | 4/5 | 1 | |||
ASB10 | ENST00000377867.7 | c.1220C>G | p.Pro407Arg | missense_variant | 5/6 | 2 | A1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000329 AC: 5AN: 152142Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000670 AC: 15AN: 223810Hom.: 0 AF XY: 0.0000410 AC XY: 5AN XY: 121834
GnomAD4 exome AF: 0.00000836 AC: 12AN: 1435386Hom.: 0 Cov.: 31 AF XY: 0.00000702 AC XY: 5AN XY: 712156
GnomAD4 genome ? AF: 0.0000329 AC: 5AN: 152142Hom.: 0 Cov.: 33 AF XY: 0.0000135 AC XY: 1AN XY: 74308
ClinVar
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Jul 26, 2022 | The c.1265C>G (p.P422R) alteration is located in exon 5 (coding exon 5) of the ASB10 gene. This alteration results from a C to G substitution at nucleotide position 1265, causing the proline (P) at amino acid position 422 to be replaced by an arginine (R). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Jul 19, 2022 | This variant has not been reported in the literature in individuals affected with ASB10-related conditions. 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 are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). This variant is present in population databases (rs566879250, gnomAD 0.06%), and has an allele count higher than expected for a pathogenic variant. This sequence change replaces proline, which is neutral and non-polar, with arginine, which is basic and polar, at codon 422 of the ASB10 protein (p.Pro422Arg). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at