Variant chr1-151055699-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM1PM2PP3_Moderate

The NM_020239.4(CDC42SE1):c.32G>A(p.Cys11Tyr) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,260 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 31)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

CDC42SE1
NM_020239.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.48

Variant links:

Genes affected

CDC42SE1 (HGNC:17719): (CDC42 small effector 1) Predicted to enable GTPase inhibitor activity. Predicted to be involved in signal transduction. Located in cell junction. [provided by Alliance of Genome Resources, Apr 2022]

CDC42SE1 links:

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ACMG classification

Classification made for transcript

Verdict is Likely_pathogenic. Variant got 6 ACMG points.

PM1

In a lipid_moiety_binding_region S-palmitoyl cysteine (size 0) in uniprot entity C42S1_HUMAN

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.901

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CDC42SE1	NM_020239.4 link	c.32G>A	p.Cys11Tyr	missense_variant	2/5	ENST00000357235.6	NP_064624.1	Q9NRR8-1
CDC42SE1	NM_001038707.2 link	c.32G>A	p.Cys11Tyr	missense_variant	3/6		NP_001033796.1	Q9NRR8-1
CDC42SE1	XM_017001847.3 link	c.32G>A	p.Cys11Tyr	missense_variant	3/6		XP_016857336.1	Q9NRR8-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CDC42SE1	ENST00000357235.6 link	c.32G>A	p.Cys11Tyr	missense_variant	2/5	1	NM_020239.4	ENSP00000349773.4		Q9NRR8-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461260

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

726902

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.0000383

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

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

Aug 27, 2024

The c.32G>A (p.C11Y) alteration is located in exon 3 (coding exon 1) of the CDC42SE1 gene. This alteration results from a G to A substitution at nucleotide position 32, causing the cysteine (C) at amino acid position 11 to be replaced by a tyrosine (Y). 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

Pathogenic

0.94

BayesDel_addAF

Pathogenic

0.44

BayesDel_noAF

Pathogenic

0.39

CADD

Uncertain

DANN

Uncertain

0.99

DEOGEN2

Uncertain

0.43

T;T;T

Eigen

Uncertain

0.32

Eigen_PC

Uncertain

0.47

FATHMM_MKL

Uncertain

0.95

LIST_S2

Uncertain

0.88

.;.;D

M_CAP

Benign

0.067

MetaRNN

Pathogenic

0.90

D;D;D

MetaSVM

Benign

-0.73

PrimateAI

Pathogenic

0.83

PROVEAN

Pathogenic

-9.2

.;D;D

REVEL

Uncertain

0.54

Sift

Uncertain

0.0030

.;D;D

Sift4G

Pathogenic

0.0

D;D;D

Polyphen

0.26

B;B;B

Vest4

0.89

MutPred

0.78

Gain of phosphorylation at C11 (P = 0.0235);Gain of phosphorylation at C11 (P = 0.0235);Gain of phosphorylation at C11 (P = 0.0235);

MVP

0.58

MPC

1.5

ClinPred

1.0

GERP RS

5.9

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.91

gMVP

0.95

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over