chr14-30605780-C-G

Position:

• chr14-30605780-C-G

Variant summary

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

The NM_017769.5(G2E3):​c.1286C>G​(p.Ser429Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: G2E3 NM_017769.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.08

Genes affected

G2E3 (HGNC:20338): (G2/M-phase specific E3 ubiquitin protein ligase) Predicted to enable ubiquitin protein ligase activity. Predicted to be involved in apoptotic process and protein ubiquitination. Predicted to act upstream of or within blastocyst development; negative regulation of intrinsic apoptotic signaling pathway; and protein polyubiquitination. Located in Golgi apparatus and cytosol. [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/exons	MANE	UniProt
G2E3	NM_017769.5	c.1286C>G	p.Ser429Cys	missense_variant	11/15	ENST00000206595.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
G2E3	ENST00000206595.11	c.1286C>G	p.Ser429Cys	missense_variant	11/15	1	NM_017769.5	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 28

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

Nov 09, 2023

The c.1286C>G (p.S429C) alteration is located in exon 11 (coding exon 10) of the G2E3 gene. This alteration results from a C to G substitution at nucleotide position 1286, causing the serine (S) at amino acid position 429 to be replaced by a cysteine (C). 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	0.12
BayesDel_addAF	Uncertain	0.024	T
BayesDel_noAF	Benign	-0.20
CADD	Pathogenic	26
DANN	Uncertain	0.99
DEOGEN2	Benign	0.092	T;T;T
Eigen	Pathogenic	0.75
Eigen_PC	Pathogenic	0.74
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Benign	0.79	T;T;T
M_CAP	Benign	0.015	T
MetaRNN	Uncertain	0.49	T;T;T
MetaSVM	Benign	-0.51	T
MutationAssessor	Uncertain	2.5	M;.;.
MutationTaster	Benign	0.87	D;D;D
PrimateAI	Uncertain	0.53	T
PROVEAN	Benign	-2.0	N;N;N
REVEL	Benign	0.25
Sift	Uncertain	0.0050	D;D;D
Sift4G	Pathogenic	0.0	D;D;D
Polyphen		1.0	D;.;.
Vest4		0.54
MutPred		0.56		Gain of catalytic residue at L430 (P = 0.0012);.;.;
MVP		0.24
MPC		1.0
ClinPred		0.95	D
GERP RS		6.0
Varity_R		0.30
gMVP		0.27

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.070		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: chr14-31074986;