chr3-46976732-T-A
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Variant summary
Our verdict is Pathogenic. Variant got 10 ACMG points: 10P and 0B. PVS1PM2
The NM_001277074.2(CCDC12):c.1A>T(p.Met1?) variant causes a start lost 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
Genomes: not found (cov: 31)
Exomes 𝑓: 0.0000028 ( 0 hom. )
Consequence
CCDC12
NM_001277074.2 start_lost
NM_001277074.2 start_lost
Scores
4
6
7
Clinical Significance
Conservation
PhyloP100: 2.30
Genes affected
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ACMG classification
Classification made for transcript
Verdict is Pathogenic. Variant got 10 ACMG points.
PVS1
Start lost variant, no new inframe start found.
PM2
Very rare variant in population databases, with high coverage;
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CCDC12 | NM_001277074.2 | c.1A>T | p.Met1? | start_lost | 1/7 | ENST00000683445.1 | |
CCDC12 | NM_144716.6 | c.40A>T | p.Met14Leu | missense_variant | 2/8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CCDC12 | ENST00000683445.1 | c.1A>T | p.Met1? | start_lost | 1/7 | NM_001277074.2 | P1 |
Frequencies
GnomAD3 genomes Cov.: 31
GnomAD3 genomes
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31
GnomAD3 exomes AF: 0.00000426 AC: 1AN: 234590Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 126986
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GnomAD4 exome AF: 0.00000275 AC: 4AN: 1453490Hom.: 0 Cov.: 34 AF XY: 0.00000277 AC XY: 2AN XY: 722268
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GnomAD4 genome Cov.: 31
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31
Bravo
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Sep 29, 2022 | 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:
Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
CADD
Uncertain
DANN
Benign
DEOGEN2
Benign
T;.;T;T
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Benign
D
LIST_S2
Uncertain
D;T;D;D
M_CAP
Uncertain
D
MetaRNN
Pathogenic
D;D;D;D
MetaSVM
Benign
T
MutationTaster
Benign
D;N;N
PrimateAI
Uncertain
T
PROVEAN
Benign
N;N;N;.
REVEL
Uncertain
Sift
Benign
T;D;T;.
Sift4G
Pathogenic
D;T;D;.
Polyphen
P;.;.;.
Vest4
MutPred
Gain of glycosylation at T5 (P = 0.0313);.;Gain of glycosylation at T5 (P = 0.0313);Gain of glycosylation at T5 (P = 0.0313);
MVP
MPC
ClinPred
D
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
Varity_R
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at