9-4701962-G-T

Variant names:

• chr9-4701962-G-T
• rs780950371
• NM_017913.4:c.846G>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.846G>T​(p.Met282Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000704 in 1,420,754 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. M282V) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 7.0e-7 (0 hom.)
• Consequence: CDC37L1 NM_017913.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.14
• 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=0.07548961).

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.846G>T	p.Met282Ile	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.846G>T	p.Met282Ile	missense	Exon 6 of 7	ENSP00000371278.3	Q7L3B6
	CDC37L1	ENST00000906225.1		c.786G>T	p.Met262Ile	missense	Exon 6 of 7	ENSP00000576284.1
	CDC37L1	ENST00000381858.5	TSL:5	c.846G>T	p.Met282Ile	missense	Exon 6 of 7	ENSP00000371282.1	B1AL69

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 7.04e-7 AC: 1 AN: 1420754 Hom.: 0 Cov.: 28 AF XY: 0.00 AC XY: 0 AN XY: 707002

African (AFR) AF: 0.00 AC: 0 AN: 30658

American (AMR) AF: 0.00 AC: 0 AN: 36294

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24710

East Asian (EAS) AF: 0.00 AC: 0 AN: 38022

South Asian (SAS) AF: 0.00 AC: 0 AN: 79944

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52388

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5564

European-Non Finnish (NFE) AF: 9.13e-7 AC: 1 AN: 1094732

Other (OTH) AF: 0.00 AC: 0 AN: 58442

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.21	T
BayesDel_noAF	Benign	-0.55
CADD	Benign	19
DANN	Benign	0.92
DEOGEN2	Benign	0.027	T
Eigen	Benign	-0.31
Eigen_PC	Benign	-0.057
FATHMM_MKL	Benign	0.64	D
LIST_S2	Benign	0.65	T
M_CAP	Benign	0.0026	T
MetaRNN	Benign	0.075	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.0	N
PhyloP100		1.1
PrimateAI	Benign	0.34	T
PROVEAN	Benign	-0.55	N
REVEL	Benign	0.097
Sift	Benign	0.51	T
Sift4G	Benign	0.47	T
Polyphen		0.0	B
Vest4		0.15
MutPred		0.55		Loss of disorder (P = 0.068)
MVP		0.19
MPC		0.15
ClinPred		0.10	T
GERP RS		4.9
Varity_R		0.052
gMVP		0.098
Mutation Taster		=96/4	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.11		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: rs780950371; hg19: chr9-4701962;