19-18768750-C-A
Variant summary
Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2
The NM_015321.3(CRTC1):c.1277C>A(p.Pro426Gln) variant causes a missense change. The variant allele was found at a frequency of 0.00000999 in 1,602,044 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign 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. P426L) has been classified as Uncertain significance.
Frequency
Consequence
NM_015321.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -6 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CRTC1 | NM_015321.3 | c.1277C>A | p.Pro426Gln | missense_variant | 10/14 | ENST00000321949.13 | |
CRTC1 | NM_001098482.2 | c.1325C>A | p.Pro442Gln | missense_variant | 11/15 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CRTC1 | ENST00000321949.13 | c.1277C>A | p.Pro426Gln | missense_variant | 10/14 | 1 | NM_015321.3 | A1 | |
CRTC1 | ENST00000338797.10 | c.1325C>A | p.Pro442Gln | missense_variant | 11/15 | 1 | P4 | ||
CRTC1 | ENST00000594658.5 | c.1154C>A | p.Pro385Gln | missense_variant | 10/14 | 1 | |||
CRTC1 | ENST00000601916.1 | c.786+3222C>A | intron_variant | 5 |
Frequencies
GnomAD3 genomes AF: 0.0000263 AC: 4AN: 152206Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.00000893 AC: 2AN: 223958Hom.: 0 AF XY: 0.00000819 AC XY: 1AN XY: 122092
GnomAD4 exome AF: 0.00000828 AC: 12AN: 1449838Hom.: 0 Cov.: 34 AF XY: 0.00000694 AC XY: 5AN XY: 720110
GnomAD4 genome AF: 0.0000263 AC: 4AN: 152206Hom.: 0 Cov.: 33 AF XY: 0.0000269 AC XY: 2AN XY: 74358
ClinVar
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Sep 14, 2023 | The c.1325C>A (p.P442Q) alteration is located in exon 11 (coding exon 11) of the CRTC1 gene. This alteration results from a C to A substitution at nucleotide position 1325, causing the proline (P) at amino acid position 442 to be replaced by a glutamine (Q). 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