7-77260184-G-C
Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong
The NM_020879.3(CCDC146):c.934G>C(p.Val312Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00011 in 1,613,936 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Synonymous variant affecting the same amino acid position (i.e. V312V) has been classified as Likely benign.
Frequency
Consequence
NM_020879.3 missense
Scores
Clinical Significance
Conservation
Genome browser will be placed here
ACMG classification
Verdict is Likely_benign. Variant got -2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CCDC146 | NM_020879.3 | c.934G>C | p.Val312Leu | missense_variant | 8/19 | ENST00000285871.5 | |
LOC102723791 | XR_927688.3 | n.380-2929C>G | intron_variant, non_coding_transcript_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CCDC146 | ENST00000285871.5 | c.934G>C | p.Val312Leu | missense_variant | 8/19 | 1 | NM_020879.3 | P1 | |
CCDC146 | ENST00000415740.6 | n.217G>C | non_coding_transcript_exon_variant | 1/11 | 1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000460 AC: 7AN: 152044Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000756 AC: 19AN: 251390Hom.: 0 AF XY: 0.0000810 AC XY: 11AN XY: 135876
GnomAD4 exome AF: 0.000117 AC: 171AN: 1461774Hom.: 0 Cov.: 33 AF XY: 0.000120 AC XY: 87AN XY: 727184
GnomAD4 genome ? AF: 0.0000460 AC: 7AN: 152162Hom.: 0 Cov.: 32 AF XY: 0.0000403 AC XY: 3AN XY: 74380
ClinVar
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Feb 21, 2024 | The c.934G>C (p.V312L) alteration is located in exon 8 (coding exon 7) of the CCDC146 gene. This alteration results from a G to C substitution at nucleotide position 934, causing the valine (V) at amino acid position 312 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