9-4701958-C-T

Variant names:

• chr9-4701958-C-T
• rs1188620156
• NM_017913.4:c.842C>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_017913.4(CDC37L1):​c.842C>T​(p.Pro281Leu) variant causes a missense change. The variant allele was found at a frequency of 0.00000281 in 1,423,444 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P281R) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000028 (0 hom.)
• Consequence: CDC37L1 NM_017913.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.01
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.15146366).

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.842C>T	p.Pro281Leu	missense	Exon 6 of 7	NP_060383.2	Q7L3B6

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CDC37L1	ENST00000381854.4	TSL:1 MANE Select	c.842C>T	p.Pro281Leu	missense	Exon 6 of 7	ENSP00000371278.3	Q7L3B6
	CDC37L1	ENST00000906225.1		c.782C>T	p.Pro261Leu	missense	Exon 6 of 7	ENSP00000576284.1
	CDC37L1	ENST00000381858.5	TSL:5	c.842C>T	p.Pro281Leu	missense	Exon 6 of 7	ENSP00000371282.1	B1AL69

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000281 AC: 4 AN: 1423444 Hom.: 0 Cov.: 28 AF XY: 0.00000141 AC XY: 1 AN XY: 708410

African (AFR) AF: 0.00 AC: 0 AN: 30842

American (AMR) AF: 0.00 AC: 0 AN: 36798

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24882

East Asian (EAS) AF: 0.00 AC: 0 AN: 38222

South Asian (SAS) AF: 0.00 AC: 0 AN: 80388

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52502

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5578

European-Non Finnish (NFE) AF: 0.00000365 AC: 4 AN: 1095630

Other (OTH) AF: 0.00 AC: 0 AN: 58602

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.088
BayesDel_addAF	Benign	-0.10	T
BayesDel_noAF	Benign	-0.39
CADD	Benign	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.051	T
Eigen	Benign	0.0026
Eigen_PC	Uncertain	0.24
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.88	D
M_CAP	Benign	0.010	T
MetaRNN	Benign	0.15	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.1	L
PhyloP100		4.0
PrimateAI	Benign	0.46	T
PROVEAN	Benign	-1.4	N
REVEL	Benign	0.13
Sift	Benign	0.044	D
Sift4G	Benign	0.11	T
Polyphen		0.27	B
Vest4		0.24
MutPred		0.47		Loss of disorder (P = 0.0162)
MVP		0.082
MPC		0.23
ClinPred		0.61	D
GERP RS		5.8
Varity_R		0.072
gMVP		0.15
Mutation Taster		=85/15	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.060		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs1188620156; hg19: chr9-4701958;