17-47981705-T-C

Variant names:

• chr17-47981705-T-C
• rs2737
• NM_176096.3:c.*203T>C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001278198.2(CDK5RAP3):​c.922T>C​(p.Ser308Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.232 in 1,532,370 control chromosomes in the GnomAD database, including 45,266 homozygotes. In-silico tool predicts a benign outcome for this variant. 5/5 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.20 (3741 hom., cov: 33)
  • Exomes 𝑓: 0.24 (41525 hom.)
• Consequence: CDK5RAP3 NM_001278198.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.01

Genes affected

CDK5RAP3 (HGNC:18673): (CDK5 regulatory subunit associated protein 3) This gene encodes a protein that has been reported to function in signaling pathways governing transcriptional regulation and cell cycle progression. It may play a role in tumorigenesis and metastasis. A pseudogene of this gene is located on the long arm of chromosome 20. Alternative splicing results in multiple transcript variants that encode different isoforms. [provided by RefSeq, May 2013]

ENSG00000263798 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.505 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CDK5RAP3	NM_176096.3	c.*203T>C		3_prime_UTR_variant	Exon 14 of 14	ENST00000338399.9	NP_788276.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CDK5RAP3	ENST00000338399.9	c.*203T>C		3_prime_UTR_variant	Exon 14 of 14	1	NM_176096.3	ENSP00000344683.4

Frequencies

GnomAD3 genomes AF: 0.196 AC: 29855 AN: 152064 Hom.: 3736 Cov.: 33

Gnomad AFR AF: 0.0683

Gnomad AMI AF: 0.212

Gnomad AMR AF: 0.238

Gnomad ASJ AF: 0.184

Gnomad EAS AF: 0.521

Gnomad SAS AF: 0.235

Gnomad FIN AF: 0.272

Gnomad MID AF: 0.171

Gnomad NFE AF: 0.225

Gnomad OTH AF: 0.233

GnomAD3 exomes AF: 0.249 AC: 35137 AN: 141246 Hom.: 4936 AF XY: 0.249 AC XY: 18883 AN XY: 75886

Gnomad AFR exome AF: 0.0592

Gnomad AMR exome AF: 0.272

Gnomad ASJ exome AF: 0.190

Gnomad EAS exome AF: 0.507

Gnomad SAS exome AF: 0.239

Gnomad FIN exome AF: 0.264

Gnomad NFE exome AF: 0.225

Gnomad OTH exome AF: 0.249

GnomAD4 exome AF: 0.236 AC: 325269 AN: 1380188 Hom.: 41525 Cov.: 33 AF XY: 0.236 AC XY: 160903 AN XY: 681180

Gnomad4 AFR exome AF: 0.0574

Gnomad4 AMR exome AF: 0.268

Gnomad4 ASJ exome AF: 0.190

Gnomad4 EAS exome AF: 0.560

Gnomad4 SAS exome AF: 0.241

Gnomad4 FIN exome AF: 0.267

Gnomad4 NFE exome AF: 0.229

Gnomad4 OTH exome AF: 0.232

GnomAD4 genome AF: 0.196 AC: 29871 AN: 152182 Hom.: 3741 Cov.: 33 AF XY: 0.201 AC XY: 14932 AN XY: 74382

Gnomad4 AFR AF: 0.0682

Gnomad4 AMR AF: 0.238

Gnomad4 ASJ AF: 0.184

Gnomad4 EAS AF: 0.522

Gnomad4 SAS AF: 0.235

Gnomad4 FIN AF: 0.272

Gnomad4 NFE AF: 0.225

Gnomad4 OTH AF: 0.235

Alfa AF: 0.209 Hom.: 1401

Bravo AF: 0.189

Asia WGS AF: 0.341 AC: 1182 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	4.8
DANN	Benign	0.62

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: rs2737; hg19: chr17-46059071; COSMIC: COSV58114512; COSMIC: COSV58114512;