Variant 11-64827372-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_017525.3(CDC42BPG):c.4177C>T(p.Leu1393Phe) variant causes a missense change. The variant allele was found at a frequency of 0.000013 in 1,461,550 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.000013 ( 0 hom. )

Consequence

CDC42BPG
NM_017525.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.74

Variant links:

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]

CDC42BPG links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.23202202).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CDC42BPG	NM_017525.3 linkuse as main transcript	c.4177C>T	p.Leu1393Phe	missense_variant	33/37	ENST00000342711.6	NP_059995.2	Q6DT37

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CDC42BPG	ENST00000342711.6 linkuse as main transcript	c.4177C>T	p.Leu1393Phe	missense_variant	33/37	1	NM_017525.3	ENSP00000345133.5		Q6DT37

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000119

AC:

AN:

251410

Hom.:

AF XY:

0.00000736

AC XY:

AN XY:

135890

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000289

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000327

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000879

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000130

AC:

AN:

1461550

Hom.:

Cov.:

AF XY:

0.00000963

AC XY:

AN XY:

727014

show subpopulations

Gnomad4 AFR exome

AF:

0.0000299

Gnomad4 AMR exome

AF:

0.0000224

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000116

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000135

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000555

Hom.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jul 12, 2022

The c.4177C>T (p.L1393F) alteration is located in exon 33 (coding exon 33) of the CDC42BPG gene. This alteration results from a C to T substitution at nucleotide position 4177, causing the leucine (L) at amino acid position 1393 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

0.24

BayesDel_addAF

Benign

-0.13

BayesDel_noAF

Benign

-0.33

CADD

Uncertain

DANN

Uncertain

0.99

DEOGEN2

Benign

0.024

Eigen

Uncertain

0.40

Eigen_PC

Uncertain

0.41

FATHMM_MKL

Uncertain

0.82

LIST_S2

Benign

0.76

M_CAP

Benign

0.030

MetaRNN

Benign

0.23

MetaSVM

Benign

-0.49

MutationAssessor

Benign

1.0

PrimateAI

Benign

0.38

PROVEAN

Benign

-1.6

REVEL

Benign

0.19

Sift

Benign

0.69

Sift4G

Benign

0.36

Polyphen

0.99

Vest4

0.40

MutPred

0.14

Loss of catalytic residue at L1393 (P = 0.0334);

MVP

0.71

MPC

0.91

ClinPred

0.52

GERP RS

4.8

Varity_R

0.098

gMVP

0.19

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over