chr9-4697180-T-C

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The ENST00000381854.4(CDC37L1):ā€‹c.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

Scores

1
5
13

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.93
Variant links:
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]

Genome browser will be placed here

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
CDC37L1NM_017913.4 linkuse as main transcriptc.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
CDC37L1ENST00000381854.4 linkuse as main transcriptc.593T>C p.Ile198Thr missense_variant 4/71 NM_017913.4 ENSP00000371278 P1
CDC37L1ENST00000381858.5 linkuse as main transcriptc.593T>C p.Ile198Thr missense_variant 4/75 ENSP00000371282

Frequencies

GnomAD3 genomes
AF:
0.0000789
AC:
12
AN:
152186
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0000241
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000262
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.000103
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.000100
AC:
25
AN:
248902
Hom.:
0
AF XY:
0.0000893
AC XY:
12
AN XY:
134422
show subpopulations
Gnomad AFR exome
AF:
0.0000619
Gnomad AMR exome
AF:
0.000206
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.000150
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.000136
AC:
193
AN:
1414722
Hom.:
0
Cov.:
23
AF XY:
0.000147
AC XY:
104
AN XY:
706592
show subpopulations
Gnomad4 AFR exome
AF:
0.0000616
Gnomad4 AMR exome
AF:
0.000203
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0000254
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.000163
Gnomad4 OTH exome
AF:
0.000102
GnomAD4 genome
AF:
0.0000788
AC:
12
AN:
152304
Hom.:
0
Cov.:
32
AF XY:
0.000107
AC XY:
8
AN XY:
74478
show subpopulations
Gnomad4 AFR
AF:
0.0000241
Gnomad4 AMR
AF:
0.000261
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000103
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.000179
Hom.:
0
Bravo
AF:
0.000102
TwinsUK
AF:
0.00
AC:
0
ALSPAC
AF:
0.000519
AC:
2
ExAC
AF:
0.0000741
AC:
9
EpiCase
AF:
0.000273
EpiControl
AF:
0.000415

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 submitterclinical testingAmbry GeneticsDec 27, 2022The 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: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
0.41
BayesDel_addAF
Benign
-0.19
T
BayesDel_noAF
Benign
-0.22
CADD
Uncertain
24
DANN
Uncertain
1.0
DEOGEN2
Benign
0.31
.;T
Eigen
Benign
-0.076
Eigen_PC
Benign
0.10
FATHMM_MKL
Pathogenic
0.99
D
LIST_S2
Benign
0.80
T;T
M_CAP
Benign
0.011
T
MetaRNN
Benign
0.38
T;T
MetaSVM
Benign
-1.1
T
MutationAssessor
Benign
1.1
.;L
MutationTaster
Benign
0.99
D;D
PrimateAI
Uncertain
0.78
T
PROVEAN
Uncertain
-2.5
D;D
REVEL
Benign
0.19
Sift
Benign
0.040
D;D
Sift4G
Uncertain
0.0070
D;D
Polyphen
0.24
.;B
Vest4
0.72
MVP
0.22
MPC
0.23
ClinPred
0.083
T
GERP RS
4.6
Varity_R
0.21
gMVP
0.52

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.0
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs200881971; hg19: chr9-4697180; API