15-68946133-C-A
Variant summary
Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3
The NM_145658.4(SPESP1):c.599C>A(p.Pro200His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,874 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. P200A) has been classified as Uncertain significance.
Frequency
Consequence
NM_145658.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 3 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SPESP1 | NM_145658.4 | c.599C>A | p.Pro200His | missense_variant | 2/2 | ENST00000310673.4 | |
NOX5 | NM_001184780.2 | c.29+15416C>A | intron_variant | ||||
NOX5 | NR_033671.3 | n.193+15416C>A | intron_variant, non_coding_transcript_variant | ||||
NOX5 | NR_033672.2 | n.193+15416C>A | intron_variant, non_coding_transcript_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SPESP1 | ENST00000310673.4 | c.599C>A | p.Pro200His | missense_variant | 2/2 | 1 | NM_145658.4 | P1 | |
SPESP1 | ENST00000560188.1 | downstream_gene_variant | 2 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD3 exomes AF: 0.00000398 AC: 1AN: 251118Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 135754
GnomAD4 exome AF: 0.00000137 AC: 2AN: 1461874Hom.: 0 Cov.: 33 AF XY: 0.00000138 AC XY: 1AN XY: 727234
GnomAD4 genome ? Cov.: 32
ClinVar
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Apr 25, 2023 | The c.599C>A (p.P200H) alteration is located in exon 2 (coding exon 2) of the SPESP1 gene. This alteration results from a C to A substitution at nucleotide position 599, causing the proline (P) at amino acid position 200 to be replaced by a histidine (H). 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