10-122836882-G-A
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_022034.6(CUZD1):c.766C>T(p.Arg256Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000217 in 1,613,998 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.00011 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000012 ( 0 hom. )
Consequence
CUZD1
NM_022034.6 missense
NM_022034.6 missense
Scores
1
2
14
Clinical Significance
Conservation
PhyloP100: 1.31
Genes affected
CUZD1 (HGNC:17937): (CUB and zona pellucida like domains 1) Predicted to be involved in trypsinogen activation. Located in membrane. [provided by Alliance of Genome Resources, Apr 2022]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 0 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
BP4
?
Computational evidence support a benign effect (MetaRNN=0.17491713).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CUZD1 | NM_022034.6 | c.766C>T | p.Arg256Trp | missense_variant | 5/9 | ENST00000392790.6 | |
FAM24B-CUZD1 | NR_037915.1 | n.1442C>T | non_coding_transcript_exon_variant | 7/11 | |||
CUZD1 | NR_037912.2 | n.629C>T | non_coding_transcript_exon_variant | 4/8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CUZD1 | ENST00000392790.6 | c.766C>T | p.Arg256Trp | missense_variant | 5/9 | 1 | NM_022034.6 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.000112 AC: 17AN: 152110Hom.: 0 Cov.: 32
GnomAD3 genomes
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GnomAD3 exomes AF: 0.0000319 AC: 8AN: 250798Hom.: 0 AF XY: 0.0000369 AC XY: 5AN XY: 135544
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GnomAD4 exome AF: 0.0000123 AC: 18AN: 1461770Hom.: 0 Cov.: 31 AF XY: 0.0000124 AC XY: 9AN XY: 727190
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GnomAD4 genome ? AF: 0.000112 AC: 17AN: 152228Hom.: 0 Cov.: 32 AF XY: 0.000121 AC XY: 9AN XY: 74438
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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 | Dec 07, 2023 | The c.766C>T (p.R256W) alteration is located in exon 5 (coding exon 5) of the CUZD1 gene. This alteration results from a C to T substitution at nucleotide position 766, causing the arginine (R) at amino acid position 256 to be replaced by a tryptophan (W). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
Cadd
Uncertain
Dann
Uncertain
DEOGEN2
Benign
T;T
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Benign
N
M_CAP
Benign
T
MetaRNN
Benign
T;T
MetaSVM
Benign
T
MutationAssessor
Benign
M;M
MutationTaster
Benign
D;D;D;D;N;N;N
PROVEAN
Pathogenic
D;D
REVEL
Benign
Sift
Uncertain
D;D
Sift4G
Benign
T;T
Polyphen
B;B
Vest4
MutPred
Loss of disorder (P = 0.0204);Loss of disorder (P = 0.0204);
MVP
MPC
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