chr9-4697180-T-C
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Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4
The ENST00000381854.4(CDC37L1):āc.593T>Cā(p.Ile198Thr) variant causes a missense change. The variant allele was found at a frequency of 0.000131 in 1,567,026 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 (ā ).
Frequency
Genomes: š 0.000079 ( 0 hom., cov: 32)
Exomes š: 0.00014 ( 0 hom. )
Consequence
CDC37L1
ENST00000381854.4 missense
ENST00000381854.4 missense
Scores
1
5
13
Clinical Significance
Conservation
PhyloP100: 5.93
Genes affected
CDC37L1 (HGNC:17179): (cell division cycle 37 like 1, HSP90 cochaperone) CDC37L1 is a cytoplasmic phosphoprotein that exists in complex with HSP90 (HSPCA; MIM 140571) as well as several other proteins involved in HSP90-mediated protein folding (Scholz et al., 2001 [PubMed 11413142]).[supplied by OMIM, Mar 2008]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 1 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.37659976).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
CDC37L1 | NM_017913.4 | c.593T>C | p.Ile198Thr | missense_variant | 4/7 | ENST00000381854.4 | NP_060383.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
CDC37L1 | ENST00000381854.4 | c.593T>C | p.Ile198Thr | missense_variant | 4/7 | 1 | NM_017913.4 | ENSP00000371278 | P1 | |
CDC37L1 | ENST00000381858.5 | c.593T>C | p.Ile198Thr | missense_variant | 4/7 | 5 | ENSP00000371282 |
Frequencies
GnomAD3 genomes AF: 0.0000789 AC: 12AN: 152186Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.000100 AC: 25AN: 248902Hom.: 0 AF XY: 0.0000893 AC XY: 12AN XY: 134422
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GnomAD4 exome AF: 0.000136 AC: 193AN: 1414722Hom.: 0 Cov.: 23 AF XY: 0.000147 AC XY: 104AN XY: 706592
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GnomAD4 genome AF: 0.0000788 AC: 12AN: 152304Hom.: 0 Cov.: 32 AF XY: 0.000107 AC XY: 8AN XY: 74478
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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 27, 2022 | The c.593T>C (p.I198T) alteration is located in exon 5 (coding exon 4) of the CDC37L1 gene. This alteration results from a T to C substitution at nucleotide position 593, causing the isoleucine (I) at amino acid position 198 to be replaced by a threonine (T). 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
Benign
T
BayesDel_noAF
Benign
CADD
Uncertain
DANN
Uncertain
DEOGEN2
Benign
.;T
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Pathogenic
D
LIST_S2
Benign
T;T
M_CAP
Benign
T
MetaRNN
Benign
T;T
MetaSVM
Benign
T
MutationAssessor
Benign
.;L
MutationTaster
Benign
D;D
PrimateAI
Uncertain
T
PROVEAN
Uncertain
D;D
REVEL
Benign
Sift
Benign
D;D
Sift4G
Uncertain
D;D
Polyphen
0.24
.;B
Vest4
MVP
MPC
0.23
ClinPred
T
GERP RS
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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