17-47975562-A-T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_176096.3(CDK5RAP3):​c.562A>T​(p.Ser188Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,458,848 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 33)
Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

CDK5RAP3
NM_176096.3 missense

Scores

7
12

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.47
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]

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.36642337).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
CDK5RAP3NM_176096.3 linkc.562A>T p.Ser188Cys missense_variant Exon 7 of 14 ENST00000338399.9 NP_788276.1 Q96JB5-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
CDK5RAP3ENST00000338399.9 linkc.562A>T p.Ser188Cys missense_variant Exon 7 of 14 1 NM_176096.3 ENSP00000344683.4 Q96JB5-1

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
AF:
6.85e-7
AC:
1
AN:
1458848
Hom.:
0
Cov.:
33
AF XY:
0.00
AC XY:
0
AN XY:
725786
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
8.99e-7
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.094
BayesDel_addAF
Benign
-0.11
T
BayesDel_noAF
Benign
-0.39
CADD
Uncertain
24
DANN
Uncertain
0.99
DEOGEN2
Benign
0.11
.;T;T;T
Eigen
Uncertain
0.39
Eigen_PC
Uncertain
0.35
FATHMM_MKL
Benign
0.49
N
LIST_S2
Uncertain
0.90
D;D;D;D
M_CAP
Benign
0.016
T
MetaRNN
Benign
0.37
T;T;T;T
MetaSVM
Benign
-0.85
T
MutationAssessor
Uncertain
2.7
.;M;.;.
PrimateAI
Benign
0.41
T
PROVEAN
Uncertain
-2.4
N;N;.;.
REVEL
Benign
0.22
Sift
Benign
0.032
D;D;.;.
Sift4G
Uncertain
0.049
D;T;D;D
Polyphen
0.97
.;D;.;.
Vest4
0.51
MutPred
0.57
.;Gain of catalytic residue at P187 (P = 0.0088);Gain of catalytic residue at P187 (P = 0.0088);.;
MVP
0.70
MPC
0.58
ClinPred
0.90
D
GERP RS
4.3
RBP_binding_hub_radar
1.1
RBP_regulation_power_radar
2.8
Varity_R
0.085
gMVP
0.18

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr17-46052928; API