NM_020239.4:c.76G>A

Variant names:

• chr1-151055105-C-T
• NM_020239.4:c.76G>A

Variant summary

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

The NM_020239.4(CDC42SE1):​c.76G>A​(p.Asp26Asn) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 30)
• Consequence: CDC42SE1 NM_020239.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.72

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]

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
CDC42SE1	NM_020239.4	c.76G>A	p.Asp26Asn	missense_variant	Exon 3 of 5	ENST00000357235.6	NP_064624.1
CDC42SE1	NM_001038707.2	c.76G>A	p.Asp26Asn	missense_variant	Exon 4 of 6		NP_001033796.1
CDC42SE1	XM_017001847.3	c.76G>A	p.Asp26Asn	missense_variant	Exon 4 of 6		XP_016857336.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CDC42SE1	ENST00000357235.6	c.76G>A	p.Asp26Asn	missense_variant	Exon 3 of 5	1	NM_020239.4	ENSP00000349773.4

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 30

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Jun 28, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.76G>A (p.D26N) alteration is located in exon 4 (coding exon 2) of the CDC42SE1 gene. This alteration results from a G to A substitution at nucleotide position 76, causing the aspartic acid (D) at amino acid position 26 to be replaced by an asparagine (N). 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	0.70
BayesDel_addAF	Benign	0.0079	T
BayesDel_noAF	Benign	-0.23
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.47	T;T;T
Eigen	Uncertain	0.20
Eigen_PC	Uncertain	0.38
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Uncertain	0.93	.;.;D
M_CAP	Benign	0.032	D
MetaRNN	Uncertain	0.69	D;D;D
MetaSVM	Benign	-0.94	T
PrimateAI	Pathogenic	0.86	D
PROVEAN	Pathogenic	-4.8	.;D;D
REVEL	Uncertain	0.33
Sift	Uncertain	0.010	.;D;D
Sift4G	Pathogenic	0.0	D;D;D
Polyphen		0.0	B;B;B
Vest4		0.84
MutPred		0.74		Gain of MoRF binding (P = 0.0573);Gain of MoRF binding (P = 0.0573);Gain of MoRF binding (P = 0.0573);
MVP		0.40
MPC		0.51
ClinPred		0.99	D
GERP RS		5.7
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.59
gMVP		0.82

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: chr1-151027581;