chr1-151055017-A-G

Position:

• chr1-151055017-A-G

Variant summary

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

The NM_020239.4(CDC42SE1):​c.164T>C​(p.Met55Thr) variant causes a missense, splice region 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. 12/21 in silico tools predict a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 31)
• Consequence: CDC42SE1 NM_020239.4 missense, splice_region
• Scores: Splicing: ADA: 0.09357
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.06

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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.36133823).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CDC42SE1	NM_020239.4	c.164T>C	p.Met55Thr	missense_variant, splice_region_variant	3/5	ENST00000357235.6	NP_064624.1
CDC42SE1	NM_001038707.2	c.164T>C	p.Met55Thr	missense_variant, splice_region_variant	4/6		NP_001033796.1
CDC42SE1	XM_017001847.3	c.164T>C	p.Met55Thr	missense_variant, splice_region_variant	4/6		XP_016857336.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CDC42SE1	ENST00000357235.6	c.164T>C	p.Met55Thr	missense_variant, splice_region_variant	3/5	1	NM_020239.4	ENSP00000349773.4

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 29

GnomAD4 genome Cov.: 31

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

Feb 27, 2024

The c.164T>C (p.M55T) alteration is located in exon 4 (coding exon 2) of the CDC42SE1 gene. This alteration results from a T to C substitution at nucleotide position 164, causing the methionine (M) at amino acid position 55 to be replaced by a threonine (T). 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	0.16
BayesDel_addAF	Uncertain	0.15	D
BayesDel_noAF	Uncertain	-0.020
CADD	Benign	20
DANN	Benign	0.94
DEOGEN2	Benign	0.027	T;T;T
Eigen	Uncertain	0.41
Eigen_PC	Uncertain	0.44
FATHMM_MKL	Uncertain	0.92	D
LIST_S2	Benign	0.63	.;.;T
M_CAP	Benign	0.0032	T
MetaRNN	Benign	0.36	T;T;T
MetaSVM	Benign	-1.0	T
PrimateAI	Uncertain	0.76	T
PROVEAN	Benign	0.020	.;N;N
REVEL	Benign	0.10
Sift	Benign	0.35	.;T;T
Sift4G	Benign	0.50	T;T;T
Polyphen		0.014	B;B;B
Vest4		0.66
MutPred		0.25		Gain of glycosylation at M55 (P = 0.0158);Gain of glycosylation at M55 (P = 0.0158);Gain of glycosylation at M55 (P = 0.0158);
MVP		0.62
MPC		0.60
ClinPred		0.85	D
GERP RS		5.7
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.11
gMVP		0.51

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.094
dbscSNV1_RF	Benign	0.21
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: chr1-151027493;