NM_001394014.1:c.5203T>G

Variant names:

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

Variant summary

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

The NM_001394014.1(CDC42BPA):​c.5203T>G​(p.Ser1735Ala) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000138 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: 0.0000014 (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>G	p.Ser1735Ala	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>G	p.Ser1735Ala	missense_variant	Exon 37 of 37	5	NM_001394014.1	ENSP00000355728.5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000138 AC: 2 AN: 1447796 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 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: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000181

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	0.10
BayesDel_addAF	Uncertain	0.089	D
BayesDel_noAF	Benign	-0.11
CADD	Pathogenic	26
DANN	Uncertain	1.0
DEOGEN2	Benign	0.073	.;T;.;.;T
Eigen	Uncertain	0.65
Eigen_PC	Uncertain	0.62
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Uncertain	0.87	D;D;D;D;D
M_CAP	Benign	0.031	D
MetaRNN	Uncertain	0.54	D;D;D;D;D
MetaSVM	Uncertain	0.00040	D
MutationAssessor	Benign	2.0	.;M;.;.;.
PrimateAI	Uncertain	0.59	T
PROVEAN	Benign	-1.1	N;N;N;.;N
REVEL	Uncertain	0.30
Sift	Benign	0.13	T;T;T;.;D
Sift4G	Benign	0.26	T;T;T;T;T
Polyphen		0.93	P;.;D;.;.
Vest4		0.39
MutPred		0.15		.;.;.;.;Loss of phosphorylation at S1680 (P = 8e-04);
MVP		0.64
MPC		0.78
ClinPred		0.94	D
GERP RS		4.9
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		2.2
Varity_R		0.26
gMVP		0.35

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;