rs375951888

Variant names:

• chr20-33374139-C-G
• rs375951888
• NM_016408.4:c.1181G>C

Your query was ambiguous. Multiple possible variants found:

• chr20-33374139-C-G
• chr20-33374139-C-T

Variant summary

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

The NM_016408.4(CDK5RAP1):​c.1181G>C​(p.Arg394Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R394H) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: CDK5RAP1 NM_016408.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.86

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

Verdict is Uncertain_significance. Variant got 2 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CDK5RAP1	NM_016408.4	c.1181G>C	p.Arg394Pro	missense_variant	Exon 9 of 14	ENST00000346416.7	NP_057492.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CDK5RAP1	ENST00000346416.7	c.1181G>C	p.Arg394Pro	missense_variant	Exon 9 of 14	1	NM_016408.4	ENSP00000217372.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

Alfa AF: 0.0000282 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.37
BayesDel_addAF	Benign	-0.0061	T
BayesDel_noAF	Benign	-0.25
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.48	.;.;T;.
Eigen	Benign	0.072
Eigen_PC	Benign	0.16
FATHMM_MKL	Benign	0.65	D
LIST_S2	Pathogenic	0.97	D;D;D;D
M_CAP	Benign	0.032	D
MetaRNN	Uncertain	0.53	D;D;D;D
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.5	.;.;M;.
PrimateAI	Benign	0.46	T
PROVEAN	Uncertain	-3.2	.;D;D;D
REVEL	Benign	0.21
Sift	Benign	0.11	.;T;T;T
Sift4G	Uncertain	0.050	T;T;T;T
Polyphen		0.024	B;B;B;P
Vest4		0.74
MutPred		0.70		.;.;Loss of MoRF binding (P = 8e-04);.;
MVP		0.53
MPC		0.87
ClinPred		0.96	D
GERP RS		2.8
Varity_R		0.63
gMVP		0.87

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.11		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs375951888; hg19: chr20-31961945;