9-4697149-C-G

Variant names:

• chr9-4697149-C-G
• rs146272968
• NM_017913.4:c.562C>G

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_017913.4(CDC37L1):​c.562C>G​(p.Leu188Val) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000692 in 1,445,522 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: CDC37L1 NM_017913.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.57

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.909

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CDC37L1	NM_017913.4	c.562C>G	p.Leu188Val	missense_variant	Exon 4 of 7	ENST00000381854.4	NP_060383.2
CDC37L1	XM_047423583.1	c.*6249C>G		downstream_gene_variant			XP_047279539.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CDC37L1	ENST00000381854.4	c.562C>G	p.Leu188Val	missense_variant	Exon 4 of 7	1	NM_017913.4	ENSP00000371278.3
CDC37L1	ENST00000381858.5	c.562C>G	p.Leu188Val	missense_variant	Exon 4 of 7	5		ENSP00000371282.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.92e-7 AC: 1 AN: 1445522 Hom.: 0 Cov.: 25 AF XY: 0.00000139 AC XY: 1 AN XY: 720134

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 9.11e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.26
BayesDel_addAF	Pathogenic	0.33	D
BayesDel_noAF	Pathogenic	0.24
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.40	.;T
Eigen	Pathogenic	0.92
Eigen_PC	Pathogenic	0.89
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.89	D;D
M_CAP	Benign	0.039	D
MetaRNN	Pathogenic	0.91	D;D
MetaSVM	Uncertain	-0.19	T
MutationAssessor	Pathogenic	3.3	.;M
PrimateAI	Uncertain	0.67	T
PROVEAN	Uncertain	-3.0	D;D
REVEL	Uncertain	0.59
Sift	Pathogenic	0.0	D;D
Sift4G	Pathogenic	0.0	D;D
Polyphen		1.0	.;D
Vest4		0.88
MutPred		0.79		Gain of phosphorylation at Y187 (P = 0.194);Gain of phosphorylation at Y187 (P = 0.194);
MVP		0.51
MPC		0.61
ClinPred		1.0	D
GERP RS		5.7
Varity_R		0.79
gMVP		0.59

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

Other links and lift over

dbSNP: rs146272968; hg19: chr9-4697149;