11-64827694-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_017525.3(CDC42BPG):c.4057C>T(p.Leu1353Phe) 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. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: CDC42BPG NM_017525.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.96

Genes affected

CDC42BPG (HGNC:29829): (CDC42 binding protein kinase gamma) Enables ATP binding activity; magnesium ion binding activity; and protein serine/threonine kinase activity. Involved in protein phosphorylation. Located in cell leading edge; centriolar satellite; and cytosol. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

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=0.41968936).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CDC42BPG	NM_017525.3	c.4057C>T	p.Leu1353Phe	missense_variant	31/37	ENST00000342711.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CDC42BPG	ENST00000342711.6	c.4057C>T	p.Leu1353Phe	missense_variant	31/37	1	NM_017525.3	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 26, 2023

The c.4057C>T (p.L1353F) alteration is located in exon 31 (coding exon 31) of the CDC42BPG gene. This alteration results from a C to T substitution at nucleotide position 4057, causing the leucine (L) at amino acid position 1353 to be replaced by a phenylalanine (F). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.26
BayesDel_addAF	Benign	-0.092	T
BayesDel_noAF	Benign	-0.37
Cadd	Uncertain	25
Dann	Uncertain	1.0
DEOGEN2	Benign	0.14	T
Eigen	Uncertain	0.51
Eigen_PC	Uncertain	0.49
FATHMM_MKL	Uncertain	0.83	D
LIST_S2	Uncertain	0.92	D
M_CAP	Benign	0.0043	T
MetaRNN	Benign	0.42	T
MetaSVM	Benign	-1.2	T
MutationAssessor	Uncertain	2.7	M
MutationTaster	Benign	1.0	D
PrimateAI	Uncertain	0.65	T
PROVEAN	Uncertain	-3.0	D
REVEL	Benign	0.22
Sift	Uncertain	0.0020	D
Sift4G	Uncertain	0.0080	D
Polyphen		0.95	P
Vest4		0.36
MutPred		0.76		Loss of sheet (P = 0.1158);
MVP		0.61
MPC		0.39
ClinPred		0.97	D
GERP RS		4.8
Varity_R		0.38
gMVP		0.51

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: chr11-64595166;