chr20-35626802-T-A
Variant summary
Our verdict is Likely pathogenic. Variant got 7 ACMG points: 7P and 0B. PVS1_StrongPM2PP3
The ENST00000437340.5(CPNE1):c.1237-2A>T variant causes a splice acceptor change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000174 in 1,613,172 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Consequence
ENST00000437340.5 splice_acceptor
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_pathogenic. Variant got 7 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CPNE1 | NM_152925.3 | c.1238A>T | p.Gln413Leu | missense_variant, splice_region_variant | 15/16 | ENST00000397443.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CPNE1 | ENST00000397443.7 | c.1238A>T | p.Gln413Leu | missense_variant, splice_region_variant | 15/16 | 5 | NM_152925.3 | P1 |
Frequencies
GnomAD3 genomes AF: 0.0000131 AC: 2AN: 152130Hom.: 0 Cov.: 31
GnomAD3 exomes AF: 0.0000319 AC: 8AN: 250820Hom.: 0 AF XY: 0.0000516 AC XY: 7AN XY: 135588
GnomAD4 exome AF: 0.0000178 AC: 26AN: 1460924Hom.: 0 Cov.: 30 AF XY: 0.0000275 AC XY: 20AN XY: 726848
GnomAD4 genome AF: 0.0000131 AC: 2AN: 152248Hom.: 0 Cov.: 31 AF XY: 0.0000269 AC XY: 2AN XY: 74444
ClinVar
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Jun 09, 2022 | The c.1253A>T (p.Q418L) alteration is located in exon 15 (coding exon 15) of the CPNE1 gene. This alteration results from a A to T substitution at nucleotide position 1253, causing the glutamine (Q) at amino acid position 418 to be replaced by a leucine (L). 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