10-100081405-G-A
Variant summary
Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate
The NM_001308.3(CPN1):c.221C>T(p.Pro74Leu) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000261 in 1,611,844 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 17/23 in silico tools predict a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★).
Frequency
Consequence
NM_001308.3 missense, splice_region
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -4 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CPN1 | NM_001308.3 | c.221C>T | p.Pro74Leu | missense_variant, splice_region_variant | 1/9 | ENST00000370418.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CPN1 | ENST00000370418.8 | c.221C>T | p.Pro74Leu | missense_variant, splice_region_variant | 1/9 | 1 | NM_001308.3 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000329 AC: 5AN: 152176Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000281 AC: 7AN: 248860Hom.: 0 AF XY: 0.0000223 AC XY: 3AN XY: 134614
GnomAD4 exome AF: 0.0000253 AC: 37AN: 1459668Hom.: 0 Cov.: 33 AF XY: 0.0000262 AC XY: 19AN XY: 726130
GnomAD4 genome ? AF: 0.0000329 AC: 5AN: 152176Hom.: 0 Cov.: 33 AF XY: 0.0000404 AC XY: 3AN XY: 74328
ClinVar
Submissions by phenotype
not specified Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Apr 25, 2023 | This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at