2-117941290-C-A
Position:
Variant summary
Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3
The NM_019044.5(CCDC93):c.1421G>T(p.Arg474Ile) variant causes a missense change. The variant allele was found at a frequency of 0.00000137 in 1,460,980 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 (no stars).
Frequency
Genomes: not found (cov: 32)
Exomes 𝑓: 0.0000014 ( 0 hom. )
Consequence
CCDC93
NM_019044.5 missense
NM_019044.5 missense
Scores
8
7
4
Clinical Significance
Conservation
PhyloP100: 7.05
Genes affected
Genome browser will be placed here
ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 3 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.812
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
CCDC93 | NM_019044.5 | c.1421G>T | p.Arg474Ile | missense_variant | 19/24 | ENST00000376300.7 | NP_061917.3 | |
CCDC93 | XM_011511359.2 | c.1418G>T | p.Arg473Ile | missense_variant | 19/24 | XP_011509661.2 | ||
CCDC93 | XM_011511361.1 | c.1133G>T | p.Arg378Ile | missense_variant | 18/23 | XP_011509663.1 | ||
CCDC93 | XM_047444816.1 | c.1022G>T | p.Arg341Ile | missense_variant | 16/21 | XP_047300772.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
CCDC93 | ENST00000376300.7 | c.1421G>T | p.Arg474Ile | missense_variant | 19/24 | 1 | NM_019044.5 | ENSP00000365477 | P4 | |
CCDC93 | ENST00000319432.9 | c.1418G>T | p.Arg473Ile | missense_variant | 19/24 | 5 | ENSP00000324135 | A1 | ||
CCDC93 | ENST00000466171.1 | n.65G>T | non_coding_transcript_exon_variant | 2/4 | 3 | |||||
CCDC93 | ENST00000437999.5 | c.*61G>T | 3_prime_UTR_variant, NMD_transcript_variant | 6/11 | 3 | ENSP00000392989 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD3 genomes
Cov.:
32
GnomAD4 exome AF: 0.00000137 AC: 2AN: 1460980Hom.: 0 Cov.: 30 AF XY: 0.00000275 AC XY: 2AN XY: 726858
GnomAD4 exome
AF:
AC:
2
AN:
1460980
Hom.:
Cov.:
30
AF XY:
AC XY:
2
AN XY:
726858
Gnomad4 AFR exome
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GnomAD4 genome Cov.: 32
GnomAD4 genome
Cov.:
32
TwinsUK
AF:
AC:
1
ALSPAC
AF:
AC:
0
ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: no assertion criteria provided
LINK: link
Submissions by phenotype
CCDC93-related condition Uncertain:1
Uncertain significance, no assertion criteria provided | clinical testing | PreventionGenetics, part of Exact Sciences | Sep 06, 2024 | The CCDC93 c.1421G>T variant is predicted to result in the amino acid substitution p.Arg474Ile. To our knowledge, this variant has not been reported in the literature or in a large population database, indicating this variant is rare. At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
CADD
Pathogenic
DANN
Uncertain
DEOGEN2
Benign
T;T
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Pathogenic
D
LIST_S2
Pathogenic
D;D
M_CAP
Benign
D
MetaRNN
Pathogenic
D;D
MetaSVM
Benign
T
MutationAssessor
Uncertain
M;.
MutationTaster
Benign
D;D
PrimateAI
Uncertain
T
PROVEAN
Pathogenic
D;D
REVEL
Uncertain
Sift
Uncertain
D;D
Sift4G
Uncertain
D;D
Polyphen
D;.
Vest4
MutPred
Loss of disorder (P = 0.0392);.;
MVP
MPC
ClinPred
D
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
Varity_R
gMVP
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at