17-47975957-T-C

Position:

• chr17-47975957-T-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_176096.3(CDK5RAP3):​c.742T>C​(p.Ser248Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: CDK5RAP3 NM_176096.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.169

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 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.24577278).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CDK5RAP3	NM_176096.3	c.742T>C	p.Ser248Pro	missense_variant	8/14	ENST00000338399.9	NP_788276.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CDK5RAP3	ENST00000338399.9	c.742T>C	p.Ser248Pro	missense_variant	8/14	1	NM_176096.3	ENSP00000344683.4

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jan 22, 2024

The c.742T>C (p.S248P) alteration is located in exon 8 (coding exon 8) of the CDK5RAP3 gene. This alteration results from a T to C substitution at nucleotide position 742, causing the serine (S) at amino acid position 248 to be replaced by a proline (P). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.19
BayesDel_addAF	Benign	-0.11	T
BayesDel_noAF	Benign	-0.40
CADD	Benign	14
DANN	Uncertain	1.0
DEOGEN2	Benign	0.013	.;T;T
Eigen	Benign	-0.17
Eigen_PC	Benign	-0.13
FATHMM_MKL	Benign	0.33	N
LIST_S2	Benign	0.84	T;T;D
M_CAP	Benign	0.014	T
MetaRNN	Benign	0.25	T;T;T
MetaSVM	Benign	-0.95	T
MutationAssessor	Benign	1.8	.;L;.
PrimateAI	Benign	0.40	T
PROVEAN	Benign	-1.2	N;N;.
REVEL	Benign	0.12
Sift	Benign	0.28	T;T;.
Sift4G	Benign	0.27	T;T;T
Polyphen		0.75	.;P;.
Vest4		0.45
MutPred		0.32		.;Gain of catalytic residue at P247 (P = 0.0133);.;
MVP		0.63
MPC		0.52
ClinPred		0.60	D
GERP RS		4.0
Varity_R		0.10
gMVP		0.40

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr17-46053323;