chr5-205542-G-A
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Variant summary
Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3
The NM_145265.3(CCDC127):c.538C>T(p.Arg180Cys) variant causes a missense change. The variant allele was found at a frequency of 0.00000889 in 1,461,726 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: 33)
Exomes 𝑓: 0.0000089 ( 0 hom. )
Consequence
CCDC127
NM_145265.3 missense
NM_145265.3 missense
Scores
8
9
2
Clinical Significance
Conservation
PhyloP100: 4.27
Genes affected
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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, 0.785
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CCDC127 | NM_145265.3 | c.538C>T | p.Arg180Cys | missense_variant | 3/3 | ENST00000296824.4 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CCDC127 | ENST00000296824.4 | c.538C>T | p.Arg180Cys | missense_variant | 3/3 | 1 | NM_145265.3 | P1 |
Frequencies
GnomAD3 genomes Cov.: 33
GnomAD3 genomes
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33
GnomAD3 exomes AF: 0.00000795 AC: 2AN: 251446Hom.: 0 AF XY: 0.00000736 AC XY: 1AN XY: 135896
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GnomAD4 exome AF: 0.00000889 AC: 13AN: 1461726Hom.: 0 Cov.: 32 AF XY: 0.00000550 AC XY: 4AN XY: 727132
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GnomAD4 genome Cov.: 33
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33
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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 | Aug 12, 2021 | The c.538C>T (p.R180C) alteration is located in exon 3 (coding exon 2) of the CCDC127 gene. This alteration results from a C to T substitution at nucleotide position 538, causing the arginine (R) at amino acid position 180 to be replaced by a cysteine (C). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
CADD
Pathogenic
DANN
Pathogenic
DEOGEN2
Benign
T
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
LIST_S2
Uncertain
D
M_CAP
Uncertain
D
MetaRNN
Pathogenic
D
MetaSVM
Uncertain
D
MutationAssessor
Pathogenic
M
MutationTaster
Benign
D
PrimateAI
Uncertain
T
PROVEAN
Pathogenic
D
REVEL
Pathogenic
Sift
Uncertain
D
Sift4G
Pathogenic
D
Polyphen
D
Vest4
MutPred
Gain of catalytic residue at P179 (P = 0.0099);
MVP
MPC
ClinPred
D
GERP RS
Varity_R
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
DS_AG_spliceai
Position offset: -5
Find out detailed SpliceAI scores and Pangolin per-transcript scores at