10-122836231-A-T
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Variant summary
Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2
The NM_022034.6(CUZD1):c.937T>A(p.Ser313Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000135 in 1,612,708 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.000092 ( 0 hom., cov: 32)
Exomes 𝑓: 0.00014 ( 3 hom. )
Consequence
CUZD1
NM_022034.6 missense
NM_022034.6 missense
Scores
18
Clinical Significance
Conservation
PhyloP100: -0.127
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 Benign. Variant got -8 ACMG points.
BP4
Computational evidence support a benign effect (MetaRNN=0.0134138465).
BS2
High Homozygotes in GnomAdExome4 at 3 AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
CUZD1 | NM_022034.6 | c.937T>A | p.Ser313Thr | missense_variant | 6/9 | ENST00000392790.6 | NP_071317.2 | |
CUZD1 | NR_037912.2 | n.800T>A | non_coding_transcript_exon_variant | 5/8 | ||||
FAM24B-CUZD1 | NR_037915.1 | n.1613T>A | non_coding_transcript_exon_variant | 8/11 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
CUZD1 | ENST00000392790.6 | c.937T>A | p.Ser313Thr | missense_variant | 6/9 | 1 | NM_022034.6 | ENSP00000376540.1 | ||
ENSG00000286088 | ENST00000368904.6 | n.*98T>A | non_coding_transcript_exon_variant | 7/10 | 1 | ENSP00000357900.2 | ||||
ENSG00000286088 | ENST00000368904.6 | n.*98T>A | 3_prime_UTR_variant | 7/10 | 1 | ENSP00000357900.2 |
Frequencies
GnomAD3 genomes AF: 0.0000920 AC: 14AN: 152144Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.000220 AC: 55AN: 249870Hom.: 0 AF XY: 0.000303 AC XY: 41AN XY: 135116
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GnomAD4 exome AF: 0.000139 AC: 203AN: 1460446Hom.: 3 Cov.: 31 AF XY: 0.000184 AC XY: 134AN XY: 726506
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GnomAD4 genome AF: 0.0000919 AC: 14AN: 152262Hom.: 0 Cov.: 32 AF XY: 0.000134 AC XY: 10AN XY: 74452
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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 | Jul 13, 2021 | The c.937T>A (p.S313T) alteration is located in exon 6 (coding exon 6) of the CUZD1 gene. This alteration results from a T to A substitution at nucleotide position 937, causing the serine (S) at amino acid position 313 to be replaced by a threonine (T). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
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Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
DEOGEN2
Benign
T;T
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Benign
N
LIST_S2
Benign
.;T
M_CAP
Benign
T
MetaRNN
Benign
T;T
MetaSVM
Benign
T
MutationAssessor
Benign
M;M
PROVEAN
Benign
N;N
REVEL
Benign
Sift
Benign
T;T
Sift4G
Benign
T;T
Polyphen
B;B
Vest4
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