Genetic Variant CDC37L1:p.Ile198Thr (chr9-4697180-T-C) – ACMG Classification: Likely_benign (-1 pts)

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 0P and 1B. BP4

The NM_017913.4(CDC37L1):c.593T>C(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 (★).

Frequency

Genomes: 𝑓 0.000079 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00014 ( 0 hom. )

Consequence

CDC37L1
NM_017913.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.93

Publications

0 publications found

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]

CDC37L1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -1 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.37659976).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_017913.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CDC37L1	NM_017913.4	MANE Select	c.593T>C	p.Ile198Thr	missense	Exon 4 of 7	NP_060383.2	Q7L3B6

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CDC37L1	ENST00000381854.4	TSL:1 MANE Select	c.593T>C	p.Ile198Thr	missense	Exon 4 of 7	ENSP00000371278.3	Q7L3B6
CDC37L1	ENST00000381858.5	TSL:5	c.593T>C	p.Ile198Thr	missense	Exon 4 of 7	ENSP00000371282.1	B1AL69
CDC37L1	ENST00000906224.1		c.593T>C	p.Ile198Thr	missense	Exon 4 of 7	ENSP00000576283.1

Frequencies

GnomAD3 genomes

AF:

0.0000789

AC:

AN:

152186

Hom.:

Cov.:

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

GnomAD2 exomes

AF:

0.000100

AC:

AN:

248902

AF XY:

0.0000893

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 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.:

Cov.:

AF XY:

0.000147

AC XY:

104

AN XY:

706592

show subpopulations

African (AFR)

AF:

0.0000616

AC:

AN:

32466

American (AMR)

AF:

0.000203

AC:

AN:

44284

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25854

East Asian (EAS)

AF:

0.0000254

AC:

AN:

39366

South Asian (SAS)

AF:

0.00

AC:

AN:

84496

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53326

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5634

European-Non Finnish (NFE)

AF:

0.000163

AC:

175

AN:

1070500

Other (OTH)

AF:

0.000102

AC:

AN:

58796

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.467

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0000788

AC:

AN:

152304

Hom.:

Cov.:

AF XY:

0.000107

AC XY:

AN XY:

74478

show subpopulations

African (AFR)

AF:

0.0000241

AC:

AN:

41574

American (AMR)

AF:

0.000261

AC:

AN:

15304

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3468

East Asian (EAS)

AF:

0.00

AC:

AN:

5190

South Asian (SAS)

AF:

0.00

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10620

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000103

AC:

AN:

67996

Other (OTH)

AF:

0.00

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.487

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.000178

Hom.:

Bravo

AF:

0.000102

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.000519

AC:

ExAC

AF:

0.0000741

AC:

EpiCase

AF:

0.000273

EpiControl

AF:

0.000415

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.41

BayesDel_addAF

Benign

-0.19

BayesDel_noAF

Benign

-0.22

CADD

Uncertain

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.31

Eigen

Benign

-0.076

Eigen_PC

Benign

0.10

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Benign

0.80

M_CAP

Benign

0.011

MetaRNN

Benign

0.38

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.1

PhyloP100

5.9

PrimateAI

Uncertain

0.78

PROVEAN

Uncertain

-2.5

REVEL

Benign

0.19

Sift

Benign

0.040

Sift4G

Uncertain

0.0070

Polyphen

0.24

Vest4

0.72

MVP

0.22

MPC

0.23

ClinPred

0.083

GERP RS

4.6

Varity_R

0.21

gMVP

0.52

Mutation Taster

=73/27

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over