Genetic Variant CDK5RAP3:n.2542T>C (chr17-47981705-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The ENST00000580287.5(CDK5RAP3):n.2542T>C variant causes a non coding transcript exon 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. 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
ENST00000580287.5 non_coding_transcript_exon

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.01

Publications

18 publications found

Variant links:

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]

CDK5RAP3 links:

ENSG00000263798 (HGNC:):

ENSG00000263798 links:

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ACMG classification

Classification was made for transcript

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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CDK5RAP3	NM_176096.3 link	c.*203T>C		3_prime_UTR_variant	Exon 14 of 14	ENST00000338399.9	NP_788276.1	Q96JB5-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CDK5RAP3	ENST00000338399.9 link	c.*203T>C		3_prime_UTR_variant	Exon 14 of 14	1	NM_176096.3	ENSP00000344683.4		Q96JB5-1

Frequencies

GnomAD3 genomes

AF:

0.196

AC:

29855

AN:

152064

Hom.:

3736

Cov.:

show subpopulations

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

show subpopulations

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.:

AF XY:

0.236

AC XY:

160903

AN XY:

681180

show subpopulations

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

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.481

Heterozygous variant carriers

12396

24791

37187

49582

61978

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

8676

17352

26028

34704

43380

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.196

AC:

29871

AN:

152182

Hom.:

3741

Cov.:

AF XY:

0.201

AC XY:

14932

AN XY:

74382

show subpopulations

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:

AN:

294

European-Non Finnish (NFE)

AF:

0.225

AC:

15307

AN:

67982

Other (OTH)

AF:

0.235

AC:

497

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1167

2334

3501

4668

5835

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

326

652

978

1304

1630

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

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 v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

CADD

Benign

4.8

(source)

DANN

Benign

0.62

PhyloP100

1.0

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over