Genetic Variant CDC37L1:p.Met282Val (chr9-4701960-A-G) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_017913.4(CDC37L1):c.844A>G(p.Met282Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000113 in 1,421,646 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. M282I) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.000011 ( 0 hom. )

Consequence

CDC37L1
NM_017913.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.0780

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 -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.042716056).

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.844A>G	p.Met282Val	missense	Exon 6 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.844A>G	p.Met282Val	missense	Exon 6 of 7	ENSP00000371278.3	Q7L3B6
CDC37L1	ENST00000906225.1		c.784A>G	p.Met262Val	missense	Exon 6 of 7	ENSP00000576284.1
CDC37L1	ENST00000381858.5	TSL:5	c.844A>G	p.Met282Val	missense	Exon 6 of 7	ENSP00000371282.1	B1AL69

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.0000273

AC:

AN:

220158

AF XY:

0.0000333

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000581

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000113

AC:

AN:

1421646

Hom.:

Cov.:

AF XY:

0.0000141

AC XY:

AN XY:

707412

show subpopulations

African (AFR)

AF:

0.0000652

AC:

AN:

30690

American (AMR)

AF:

0.00

AC:

AN:

36376

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

24762

East Asian (EAS)

AF:

0.00

AC:

AN:

38090

South Asian (SAS)

AF:

0.00

AC:

AN:

80054

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52442

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5574

European-Non Finnish (NFE)

AF:

0.0000119

AC:

AN:

1095166

Other (OTH)

AF:

0.0000171

AC:

AN:

58492

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.488

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

Cov.:

Alfa

AF:

0.0000314

Hom.:

Bravo

AF:

0.00000378

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.0000330

AC:

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

Benign

0.052

BayesDel_addAF

Benign

-0.34

BayesDel_noAF

Benign

-0.56

CADD

Benign

6.0

(source)

DANN

Benign

0.41

DEOGEN2

Benign

0.026

Eigen

Benign

-0.66

Eigen_PC

Benign

-0.52

FATHMM_MKL

Benign

0.44

LIST_S2

Benign

0.60

M_CAP

Benign

0.0062

MetaRNN

Benign

0.043

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.4

PhyloP100

0.078

PrimateAI

Benign

0.31

PROVEAN

Benign

-0.18

REVEL

Benign

0.060

Sift

Benign

1.0

Sift4G

Benign

1.0

Polyphen

0.0

Vest4

0.13

MVP

0.23

MPC

0.14

ClinPred

0.014

GERP RS

-0.63

Varity_R

0.028

gMVP

0.12

Mutation Taster

=96/4

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over