Variant 8-28023337-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001010906.2(NUGGC):c.2371C>A(p.Pro791Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000868 in 1,613,576 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000026 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000068 ( 0 hom. )

Consequence

NUGGC
NM_001010906.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.770

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.028993458).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
NUGGC	NM_001010906.2 linkuse as main transcript	c.2371C>A	p.Pro791Thr	missense_variant	19/19	ENST00000413272.7	NP_001010906.1
NUGGC	XM_011544523.3 linkuse as main transcript	c.2443C>A	p.Pro815Thr	missense_variant	19/19		XP_011542825.1
NUGGC	XM_011544524.4 linkuse as main transcript	c.2443C>A	p.Pro815Thr	missense_variant	19/19		XP_011542826.1
NUGGC	XM_011544525.2 linkuse as main transcript	c.1210C>A	p.Pro404Thr	missense_variant	11/11		XP_011542827.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NUGGC	ENST00000413272.7 linkuse as main transcript	c.2371C>A	p.Pro791Thr	missense_variant	19/19	5	NM_001010906.2	ENSP00000408697	P1

Frequencies

GnomAD3 genomes

AF:

0.0000263

AC:

AN:

152154

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000578

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.0000443

AC:

AN:

248264

Hom.:

AF XY:

0.0000371

AC XY:

AN XY:

134672

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000614

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000684

AC:

AN:

1461304

Hom.:

Cov.:

AF XY:

0.00000688

AC XY:

AN XY:

726932

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000227

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

AF:

0.0000263

AC:

AN:

152272

Hom.:

Cov.:

AF XY:

0.0000134

AC XY:

AN XY:

74456

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000579

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.000473

Bravo

AF:

0.0000302

ExAC

AF:

0.0000248

AC:

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

Jan 03, 2024

The c.2371C>A (p.P791T) alteration is located in exon 19 (coding exon 18) of the NUGGC gene. This alteration results from a C to A substitution at nucleotide position 2371, causing the proline (P) at amino acid position 791 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

0.067

BayesDel_addAF

Benign

-0.50

BayesDel_noAF

Benign

-0.59

CADD

Benign

DANN

Benign

0.94

DEOGEN2

Benign

0.0043

Eigen

Benign

-1.0

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.069

LIST_S2

Benign

0.54

M_CAP

Benign

0.0050

MetaRNN

Benign

0.029

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.69

MutationTaster

Benign

1.0

N;N

PrimateAI

Benign

0.30

PROVEAN

Benign

-1.4

REVEL

Benign

0.018

Sift

Benign

0.036

Sift4G

Benign

0.11

Polyphen

0.19

Vest4

0.21

MVP

0.040

MPC

0.20

ClinPred

0.058

GERP RS

-0.70

Varity_R

0.046

gMVP

0.21

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over