Variant 8-28029370-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001010906.2(NUGGC):c.2050G>A(p.Glu684Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000205 in 1,460,412 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 31)

Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

NUGGC
NM_001010906.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.96

Variant links:

Genes affected

NUGGC (HGNC:33550): (nuclear GTPase, germinal center associated) Enables GTPase activity. Involved in cellular response to lipopolysaccharide; negative regulation of apoptotic process; and regulation of nuclear cell cycle DNA replication. Predicted to be located in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

NUGGC links:

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ACMG classification

Classification made for transcript

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=0.20295742).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
NUGGC	NM_001010906.2 linkuse as main transcript	c.2050G>A	p.Glu684Lys	missense_variant	17/19	ENST00000413272.7	NP_001010906.1
NUGGC	XM_011544523.3 linkuse as main transcript	c.2122G>A	p.Glu708Lys	missense_variant	17/19		XP_011542825.1
NUGGC	XM_011544524.4 linkuse as main transcript	c.2122G>A	p.Glu708Lys	missense_variant	17/19		XP_011542826.1
NUGGC	XM_011544525.2 linkuse as main transcript	c.889G>A	p.Glu297Lys	missense_variant	9/11		XP_011542827.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NUGGC	ENST00000413272.7 linkuse as main transcript	c.2050G>A	p.Glu684Lys	missense_variant	17/19	5	NM_001010906.2	ENSP00000408697	P1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000205

AC:

AN:

1460412

Hom.:

Cov.:

AF XY:

0.00000275

AC XY:

AN XY:

726302

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000349

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

Nov 02, 2023

The c.2050G>A (p.E684K) alteration is located in exon 17 (coding exon 16) of the NUGGC gene. This alteration results from a G to A substitution at nucleotide position 2050, causing the glutamic acid (E) at amino acid position 684 to be replaced by a lysine (K). 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

0.23

BayesDel_addAF

Benign

-0.055

BayesDel_noAF

Benign

-0.32

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.00011

Eigen

Benign

-0.24

Eigen_PC

Benign

-0.077

FATHMM_MKL

Benign

0.66

LIST_S2

Uncertain

0.86

M_CAP

Benign

0.011

MetaRNN

Benign

0.20

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.9

MutationTaster

Benign

0.97

D;D

PrimateAI

Uncertain

0.61

PROVEAN

Benign

-0.26

REVEL

Benign

0.14

Sift

Benign

0.19

Sift4G

Uncertain

0.018

Polyphen

0.032

Vest4

0.55

MutPred

0.32

Gain of methylation at E684 (P = 0.0025);

MVP

0.12

MPC

0.20

ClinPred

0.47

GERP RS

5.6

Varity_R

0.13

gMVP

0.22

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