17-47981705-T-C

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 18 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001278198.2. 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
	CDK5RAP3	NM_176096.3	MANE Select	c.*203T>C		3_prime_UTR	Exon 14 of 14	NP_788276.1	Q96JB5-1
	CDK5RAP3	NM_001278198.2		c.922T>C	p.Ser308Pro	missense	Exon 13 of 13	NP_001265127.1
	CDK5RAP3	NM_001278197.2		c.*203T>C		3_prime_UTR	Exon 14 of 14	NP_001265126.1	Q96JB5-4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CDK5RAP3	ENST00000338399.9	TSL:1 MANE Select	c.*203T>C		3_prime_UTR	Exon 14 of 14	ENSP00000344683.4	Q96JB5-1
	CDK5RAP3	ENST00000580287.5	TSL:1	n.2542T>C		non_coding_transcript_exon	Exon 13 of 13
	CDK5RAP3	ENST00000584063.5	TSL:1	n.2692T>C		non_coding_transcript_exon	Exon 12 of 12

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

GnomAD2 exomes AF: 0.249 AC: 35137 AN: 141246 AF XY: 0.249

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 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

African (AFR) AF: 0.0574 AC: 1808 AN: 31522

American (AMR) AF: 0.268 AC: 9545 AN: 35560

Ashkenazi Jewish (ASJ) AF: 0.190 AC: 4750 AN: 25046

East Asian (EAS) AF: 0.560 AC: 19841 AN: 35442

South Asian (SAS) AF: 0.241 AC: 18893 AN: 78544

European-Finnish (FIN) AF: 0.267 AC: 9210 AN: 34512

Middle Eastern (MID) AF: 0.202 AC: 1149 AN: 5680

European-Non Finnish (NFE) AF: 0.229 AC: 246718 AN: 1076208

Other (OTH) AF: 0.232 AC: 13355 AN: 57674

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

African (AFR) AF: 0.0682 AC: 2835 AN: 41556

American (AMR) AF: 0.238 AC: 3640 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.184 AC: 638 AN: 3472

East Asian (EAS) AF: 0.522 AC: 2698 AN: 5172

South Asian (SAS) AF: 0.235 AC: 1135 AN: 4830

European-Finnish (FIN) AF: 0.272 AC: 2873 AN: 10574

Middle Eastern (MID) AF: 0.187 AC: 55 AN: 294

European-Non Finnish (NFE) AF: 0.225 AC: 15307 AN: 67982

Other (OTH) AF: 0.235 AC: 497 AN: 2116

Alfa AF: 0.204 Hom.: 1409

Bravo AF: 0.189

Asia WGS AF: 0.341 AC: 1182 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	4.8
DANN	Benign	0.62
PhyloP100		1.0
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

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