20-33394043-T-C

Variant names:

• chr20-33394043-T-C
• rs291700
• NM_016408.4:c.432A>G

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_016408.4(CDK5RAP1):​c.432A>G​(p.Thr144Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.665 in 1,587,612 control chromosomes in the GnomAD database, including 354,286 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 0.63 (30275 hom., cov: 32)
  • Exomes 𝑓: 0.67 (324011 hom.)
• Consequence: CDK5RAP1 NM_016408.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.42
• Publications: 37 publications found

Genes affected

CDK5RAP1 (HGNC:15880): (CDK5 regulatory subunit associated protein 1) This gene encodes a regulator of cyclin-dependent kinase 5 activity. This protein has also been reported to modify RNA by adding a methylthio-group and may thus have a dual function as an RNA methylthiotransferase and as an inhibitor of cyclin-dependent kinase 5 activity. Alternative splicing results in multiple transcript variants that encode different isoforms. [provided by RefSeq, May 2013]

ACMG classification

Our verdict: Benign. The variant received -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BP7: Synonymous conserved (PhyloP=-1.42 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.685 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_016408.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CDK5RAP1	NM_016408.4	MANE Select	c.432A>G	p.Thr144Thr	synonymous	Exon 4 of 14	NP_057492.2
	CDK5RAP1	NM_001365728.1		c.432A>G	p.Thr144Thr	synonymous	Exon 4 of 15	NP_001352657.1
	CDK5RAP1	NM_016082.4		c.435A>G	p.Thr145Thr	synonymous	Exon 4 of 14	NP_057166.4

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CDK5RAP1	ENST00000346416.7	TSL:1 MANE Select	c.432A>G	p.Thr144Thr	synonymous	Exon 4 of 14	ENSP00000217372.2
	CDK5RAP1	ENST00000339269.5	TSL:1	c.432A>G	p.Thr144Thr	synonymous	Exon 4 of 13	ENSP00000341840.5
	CDK5RAP1	ENST00000357886.8	TSL:5	c.432A>G	p.Thr144Thr	synonymous	Exon 4 of 15	ENSP00000350558.4

Frequencies

GnomAD3 genomes AF: 0.626 AC: 95125 AN: 151926 Hom.: 30254 Cov.: 32

Gnomad AFR AF: 0.527

Gnomad AMI AF: 0.698

Gnomad AMR AF: 0.591

Gnomad ASJ AF: 0.690

Gnomad EAS AF: 0.583

Gnomad SAS AF: 0.694

Gnomad FIN AF: 0.608

Gnomad MID AF: 0.665

Gnomad NFE AF: 0.690

Gnomad OTH AF: 0.636

GnomAD2 exomes AF: 0.644 AC: 161193 AN: 250448 AF XY: 0.655

Gnomad AFR exome AF: 0.522

Gnomad AMR exome AF: 0.536

Gnomad ASJ exome AF: 0.699

Gnomad EAS exome AF: 0.578

Gnomad FIN exome AF: 0.609

Gnomad NFE exome AF: 0.693

Gnomad OTH exome AF: 0.667

GnomAD4 exome AF: 0.670 AC: 961166 AN: 1435568 Hom.: 324011 Cov.: 29 AF XY: 0.672 AC XY: 480812 AN XY: 715980

African (AFR) AF: 0.512 AC: 16915 AN: 33014

American (AMR) AF: 0.543 AC: 24248 AN: 44678

Ashkenazi Jewish (ASJ) AF: 0.700 AC: 18180 AN: 25956

East Asian (EAS) AF: 0.571 AC: 22618 AN: 39602

South Asian (SAS) AF: 0.689 AC: 59078 AN: 85720

European-Finnish (FIN) AF: 0.617 AC: 32899 AN: 53318

Middle Eastern (MID) AF: 0.658 AC: 3764 AN: 5720

European-Non Finnish (NFE) AF: 0.684 AC: 744383 AN: 1088064

Other (OTH) AF: 0.657 AC: 39081 AN: 59496

GnomAD4 genome AF: 0.626 AC: 95182 AN: 152044 Hom.: 30275 Cov.: 32 AF XY: 0.624 AC XY: 46378 AN XY: 74294

African (AFR) AF: 0.527 AC: 21869 AN: 41468

American (AMR) AF: 0.591 AC: 9018 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.690 AC: 2396 AN: 3472

East Asian (EAS) AF: 0.583 AC: 3021 AN: 5182

South Asian (SAS) AF: 0.694 AC: 3348 AN: 4822

European-Finnish (FIN) AF: 0.608 AC: 6412 AN: 10542

Middle Eastern (MID) AF: 0.673 AC: 198 AN: 294

European-Non Finnish (NFE) AF: 0.690 AC: 46941 AN: 67982

Other (OTH) AF: 0.639 AC: 1344 AN: 2102

Alfa AF: 0.663 Hom.: 100354

Bravo AF: 0.617

Asia WGS AF: 0.662 AC: 2301 AN: 3478

EpiCase AF: 0.680

EpiControl AF: 0.690

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	3.4
DANN	Benign	0.47
PhyloP100		-1.4
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.12		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: rs291700; hg19: chr20-31981849; COSMIC: COSV59426897;