rs1841401387

Variant names:

• chr9-4701906-G-A
• NM_017913.4:c.790G>A

Your query was ambiguous. Multiple possible variants found:

• chr9-4701906-G-A
• chr9-4701906-G-C
• chr9-4701906-G-T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_017913.4(CDC37L1):​c.790G>A​(p.Glu264Lys) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000688 in 1,452,436 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. E264Q) has been classified as Uncertain significance.

• 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: 7.86

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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CDC37L1	NM_017913.4	c.790G>A	p.Glu264Lys	missense_variant	Exon 6 of 7	ENST00000381854.4	NP_060383.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CDC37L1	ENST00000381854.4	c.790G>A	p.Glu264Lys	missense_variant	Exon 6 of 7	1	NM_017913.4	ENSP00000371278.3
CDC37L1	ENST00000381858.5	c.790G>A	p.Glu264Lys	missense_variant	Exon 6 of 7	5		ENSP00000371282.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.88e-7 AC: 1 AN: 1452436 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 722620

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: 9.02e-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	Uncertain	0.37
BayesDel_addAF	Pathogenic	0.17	D
BayesDel_noAF	Uncertain	0.010
CADD	Pathogenic	27
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.27	.;T
Eigen	Pathogenic	0.78
Eigen_PC	Pathogenic	0.81
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Pathogenic	0.99	D;D
M_CAP	Benign	0.032	D
MetaRNN	Uncertain	0.74	D;D
MetaSVM	Benign	-0.92	T
MutationAssessor	Uncertain	2.2	.;M
PrimateAI	Uncertain	0.73	T
PROVEAN	Uncertain	-2.4	N;N
REVEL	Uncertain	0.38
Sift	Benign	0.064	T;T
Sift4G	Uncertain	0.0090	D;D
Polyphen		1.0	.;D
Vest4		0.74
MutPred		0.56		Gain of MoRF binding (P = 0.0049);Gain of MoRF binding (P = 0.0049);
MVP		0.26
MPC		0.64
ClinPred		0.87	D
GERP RS		6.2
Varity_R		0.55
gMVP		0.33

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.070		Details are displayed if max score is > 0.2

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr9-4701906;