chr14-30605596-A-G

Position:

• chr14-30605596-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_017769.5(G2E3):​c.1102A>G​(p.Lys368Glu) variant causes a missense 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. 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: 2.12

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.21495125).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
G2E3	NM_017769.5	c.1102A>G	p.Lys368Glu	missense_variant	11/15	ENST00000206595.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
G2E3	ENST00000206595.11	c.1102A>G	p.Lys368Glu	missense_variant	11/15	1	NM_017769.5	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 24

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

Apr 07, 2023

The c.1102A>G (p.K368E) alteration is located in exon 11 (coding exon 10) of the G2E3 gene. This alteration results from a A to G substitution at nucleotide position 1102, causing the lysine (K) at amino acid position 368 to be replaced by a glutamic acid (E). 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	0.15
BayesDel_addAF	Benign	-0.074	T
BayesDel_noAF	Benign	-0.34
CADD	Benign	20
DANN	Uncertain	1.0
DEOGEN2	Benign	0.034	T;T;T
Eigen	Uncertain	0.30
Eigen_PC	Uncertain	0.39
FATHMM_MKL	Uncertain	0.90	D
LIST_S2	Benign	0.78	T;T;T
M_CAP	Benign	0.0089	T
MetaRNN	Benign	0.21	T;T;T
MetaSVM	Benign	-0.99	T
MutationAssessor	Uncertain	2.5	M;.;.
MutationTaster	Benign	0.99	N;N;N
PrimateAI	Benign	0.45	T
PROVEAN	Benign	-0.30	N;N;N
REVEL	Benign	0.14
Sift	Benign	0.13	T;T;T
Sift4G	Benign	0.13	T;T;T
Polyphen		0.92	P;.;.
Vest4		0.41
MutPred		0.51		Loss of MoRF binding (P = 0.0067);.;.;
MVP		0.25
MPC		0.79
ClinPred		0.81	D
GERP RS		5.7
Varity_R		0.11
gMVP		0.50

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.

Other links and lift over

hg19: chr14-31074802;