3-46976732-T-A
Variant summary
Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2PP3_Strong
The NM_144716.6(CCDC12):c.40A>T(p.Met14Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000275 in 1,453,490 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 (★).
Frequency
Consequence
NM_144716.6 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_pathogenic. Variant got 6 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
CCDC12 | NM_001277074.2 | c.1A>T | p.Met1? | initiator_codon_variant | Exon 1 of 7 | ENST00000683445.1 | NP_001264003.1 | |
CCDC12 | NM_144716.6 | c.40A>T | p.Met14Leu | missense_variant | Exon 2 of 8 | NP_653317.2 | ||
CCDC12 | NR_102269.2 | n.-231A>T | upstream_gene_variant |
Ensembl
Frequencies
GnomAD3 genomes Cov.: 31
GnomAD3 exomes AF: 0.00000426 AC: 1AN: 234590Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 126986
GnomAD4 exome AF: 0.00000275 AC: 4AN: 1453490Hom.: 0 Cov.: 34 AF XY: 0.00000277 AC XY: 2AN XY: 722268
GnomAD4 genome Cov.: 31
ClinVar
Submissions by phenotype
not specified Uncertain:1
The c.40A>T (p.M14L) alteration is located in exon 1 (coding exon 1) of the CCDC12 gene. This alteration results from a A to T substitution at nucleotide position 40, causing the methionine (M) at amino acid position 14 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