17-47975578-T-A

Variant names:

• chr17-47975578-T-A
• rs780584998
• NM_176096.3:c.578T>A

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_001278198.2(CDK5RAP3):​c.-313T>A variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000686 in 1,458,068 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: CDK5RAP3 NM_001278198.2 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.46
• Publications: 0 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: Uncertain_significance. The variant received 2 ACMG points.

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

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.578T>A	p.Ile193Asn	missense	Exon 7 of 14	NP_788276.1	Q96JB5-1
	CDK5RAP3	NM_001278198.2		c.-313T>A		5_prime_UTR_premature_start_codon_gain	Exon 6 of 13	NP_001265127.1
	CDK5RAP3	NM_001278216.2		c.-313T>A		5_prime_UTR_premature_start_codon_gain	Exon 6 of 12	NP_001265145.1	Q96JB5-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CDK5RAP3	ENST00000338399.9	TSL:1 MANE Select	c.578T>A	p.Ile193Asn	missense	Exon 7 of 14	ENSP00000344683.4	Q96JB5-1
	CDK5RAP3	ENST00000580287.5	TSL:1	n.1308T>A		non_coding_transcript_exon	Exon 6 of 13
	CDK5RAP3	ENST00000584063.5	TSL:1	n.1331T>A		non_coding_transcript_exon	Exon 6 of 12

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.86e-7 AC: 1 AN: 1458068 Hom.: 0 Cov.: 33 AF XY: 0.00000138 AC XY: 1 AN XY: 725438

African (AFR) AF: 0.00 AC: 0 AN: 33478

American (AMR) AF: 0.00 AC: 0 AN: 44716

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39698

South Asian (SAS) AF: 0.00 AC: 0 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 49666

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 8.99e-7 AC: 1 AN: 1111984

Other (OTH) AF: 0.00 AC: 0 AN: 60364

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.49
BayesDel_addAF	Benign	-0.064	T
BayesDel_noAF	Benign	-0.33
CADD	Benign	19
DANN	Uncertain	0.98
DEOGEN2	Benign	0.23	T
Eigen	Benign	-0.11
Eigen_PC	Benign	-0.084
FATHMM_MKL	Uncertain	0.88	D
LIST_S2	Uncertain	0.88	D
M_CAP	Benign	0.024	T
MetaRNN	Uncertain	0.43	T
MetaSVM	Benign	-0.93	T
MutationAssessor	Uncertain	2.8	M
PhyloP100		1.5
PrimateAI	Benign	0.42	T
PROVEAN	Uncertain	-2.5	D
REVEL	Benign	0.16
Sift	Benign	0.075	T
Sift4G	Benign	0.061	T
Polyphen		0.56	P
Vest4		0.74
MutPred		0.70		Gain of disorder (P = 0.0107)
MVP		0.63
MPC		0.62
ClinPred		0.96	D
GERP RS		3.2
RBP_binding_hub_radar		1.1
RBP_regulation_power_radar		2.2
Varity_R		0.17
gMVP		0.70
Mutation Taster		=65/35	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs780584998; hg19: chr17-46052944;