7-5919879-G-A
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Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 0P and 2B. BP4_Moderate
The NM_015622.6(CCZ1):c.1019G>A(p.Arg340Gln) variant causes a missense change. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.000060 ( 0 hom., cov: 26)
Exomes 𝑓: 0.000049 ( 0 hom. )
Failed GnomAD Quality Control
Consequence
CCZ1
NM_015622.6 missense
NM_015622.6 missense
Scores
3
13
Clinical Significance
Conservation
PhyloP100: 5.99
Genes affected
CCZ1 (HGNC:21691): (CCZ1 homolog, vacuolar protein trafficking and biogenesis associated) Enables guanyl-nucleotide exchange factor activity. Predicted to be involved in vesicle-mediated transport. Located in intracellular membrane-bounded organelle. Part of Mon1-Ccz1 complex. [provided by Alliance of Genome Resources, Apr 2022]
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ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -2 ACMG points.
BP4
Computational evidence support a benign effect (MetaRNN=0.2538249).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
CCZ1 | NM_015622.6 | c.1019G>A | p.Arg340Gln | missense_variant | 12/15 | ENST00000325974.9 | NP_056437.4 | |
CCZ1 | XM_047420465.1 | c.955-3508G>A | intron_variant | XP_047276421.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
CCZ1 | ENST00000325974.9 | c.1019G>A | p.Arg340Gln | missense_variant | 12/15 | 1 | NM_015622.6 | ENSP00000325681 | P1 | |
CCZ1 | ENST00000628813.2 | c.*688G>A | 3_prime_UTR_variant | 11/14 | 2 | ENSP00000486988 | ||||
CCZ1 | ENST00000474507.1 | n.2154G>A | non_coding_transcript_exon_variant | 1/4 | 2 |
Frequencies
GnomAD3 genomes AF: 0.0000602 AC: 9AN: 149488Hom.: 0 Cov.: 26
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GnomAD3 exomes AF: 0.0000454 AC: 11AN: 242220Hom.: 0 AF XY: 0.0000381 AC XY: 5AN XY: 131178
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GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.0000494 AC: 72AN: 1457394Hom.: 0 Cov.: 35 AF XY: 0.0000565 AC XY: 41AN XY: 725088
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GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.0000602 AC: 9AN: 149488Hom.: 0 Cov.: 26 AF XY: 0.0000686 AC XY: 5AN XY: 72858
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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 | Jan 30, 2024 | The c.1019G>A (p.R340Q) alteration is located in exon 12 (coding exon 12) of the CCZ1 gene. This alteration results from a G to A substitution at nucleotide position 1019, causing the arginine (R) at amino acid position 340 to be replaced by a glutamine (Q). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Uncertain
DANN
Uncertain
DEOGEN2
Benign
T
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Uncertain
D
M_CAP
Benign
T
MetaRNN
Benign
T
MetaSVM
Benign
T
MutationTaster
Benign
D;D
PrimateAI
Uncertain
T
PROVEAN
Benign
N
REVEL
Benign
Sift
Benign
T
Sift4G
Benign
T
Vest4
MutPred
Loss of helix (P = 0.1706);
MVP
ClinPred
T
GERP RS
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