NM_001394014.1:c.5203T>C

Variant names:

• chr1-226994330-A-G
• NM_001394014.1:c.5203T>C

Variant summary

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

The NM_001394014.1(CDC42BPA):​c.5203T>C​(p.Ser1735Pro) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000691 in 1,447,796 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. S1735T) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: CDC42BPA NM_001394014.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 8.59

Genes affected

CDC42BPA (HGNC:1737): (CDC42 binding protein kinase alpha) The protein encoded by this gene is a member of the serine/threonine protein kinase family. This kinase contains multiple functional domains. Its kinase domain is highly similar to that of the myotonic dystrophy protein kinase (DMPK). This kinase also contains a Rac interactive binding (CRIB) domain, and has been shown to bind CDC42. It may function as a CDC42 downstream effector mediating CDC42 induced peripheral actin formation, and promoting cytoskeletal reorganization. Multiple alternatively spliced transcript variants have been described. [provided by RefSeq, Sep 2018]

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
CDC42BPA	NM_001394014.1	c.5203T>C	p.Ser1735Pro	missense_variant	Exon 37 of 37	ENST00000366766.8	NP_001380943.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CDC42BPA	ENST00000366766.8	c.5203T>C	p.Ser1735Pro	missense_variant	Exon 37 of 37	5	NM_001394014.1	ENSP00000355728.5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.91e-7 AC: 1 AN: 1447796 Hom.: 0 Cov.: 31 AF XY: 0.00000139 AC XY: 1 AN XY: 718796

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: 0.0000119

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.15
BayesDel_addAF	Uncertain	0.12	D
BayesDel_noAF	Uncertain	-0.070
CADD	Pathogenic	27
DANN	Uncertain	1.0
DEOGEN2	Benign	0.34	.;T;.;.;T
Eigen	Pathogenic	0.70
Eigen_PC	Pathogenic	0.67
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Uncertain	0.92	D;D;D;D;D
M_CAP	Benign	0.040	D
MetaRNN	Uncertain	0.56	D;D;D;D;D
MetaSVM	Uncertain	0.14	D
MutationAssessor	Benign	2.0	.;M;.;.;.
PrimateAI	Uncertain	0.61	T
PROVEAN	Benign	-2.3	N;N;N;.;N
REVEL	Uncertain	0.40
Sift	Uncertain	0.0070	D;T;D;.;D
Sift4G	Uncertain	0.026	D;D;D;D;D
Polyphen		1.0	D;.;D;.;.
Vest4		0.40
MutPred		0.23		.;.;.;.;Loss of phosphorylation at S1680 (P = 8e-04);
MVP		0.59
MPC		0.98
ClinPred		0.97	D
GERP RS		4.9
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		2.2
Varity_R		0.63
gMVP		0.42

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: chr1-227182031;