chr17-47975957-T-C

Variant names:

• chr17-47975957-T-C
• NM_176096.3:c.742T>C

Variant summary

Our verdict is Uncertain significance. The variant received 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. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. S248C) has been classified 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
• 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 0 ACMG points.

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_176096.3. 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.742T>C	p.Ser248Pro	missense	Exon 8 of 14	NP_788276.1	Q96JB5-1
	CDK5RAP3	NM_001278197.2		c.817T>C	p.Ser273Pro	missense	Exon 8 of 14	NP_001265126.1	Q96JB5-4
	CDK5RAP3	NM_001278217.2		c.481T>C	p.Ser161Pro	missense	Exon 7 of 13	NP_001265146.1	Q96JB5-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CDK5RAP3	ENST00000338399.9	TSL:1 MANE Select	c.742T>C	p.Ser248Pro	missense	Exon 8 of 14	ENSP00000344683.4	Q96JB5-1
	CDK5RAP3	ENST00000580287.5	TSL:1	n.1687T>C		non_coding_transcript_exon	Exon 6 of 13
	CDK5RAP3	ENST00000584063.5	TSL:1	n.1710T>C		non_coding_transcript_exon	Exon 6 of 12

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 33

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

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
Eigen	Benign	-0.17
Eigen_PC	Benign	-0.13
FATHMM_MKL	Benign	0.33	N
LIST_S2	Benign	0.84	T
M_CAP	Benign	0.014	T
MetaRNN	Benign	0.25	T
MetaSVM	Benign	-0.95	T
MutationAssessor	Benign	1.8	L
PhyloP100		0.17
PrimateAI	Benign	0.40	T
PROVEAN	Benign	-1.2	N
REVEL	Benign	0.12
Sift	Benign	0.28	T
Sift4G	Benign	0.27	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

Other links and lift over

hg19: chr17-46053323;