dbSNP rs7817227: NUGGC:p.Gln328Leu (chr8-28060540-T-A) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001010906.2(NUGGC):c.983A>T(p.Gln328Leu) 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. 16/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 31)

Exomes 𝑓: 0.0000021 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

NUGGC
NM_001010906.2 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.525

Publications

26 publications found

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 was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.13677788).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001010906.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NUGGC	NM_001010906.2	MANE Select	c.983A>T	p.Gln328Leu	missense	Exon 8 of 19	NP_001010906.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NUGGC	ENST00000413272.7	TSL:5 MANE Select	c.983A>T	p.Gln328Leu	missense	Exon 8 of 19	ENSP00000408697.2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.0000121

AC:

AN:

248906

AF XY:

0.0000148

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.0000994

Gnomad EAS exome

AF:

0.0000557

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000886

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.00000205

AC:

AN:

1461522

Hom.:

Cov.:

AF XY:

0.00000275

AC XY:

AN XY:

727036

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33472

American (AMR)

AF:

0.00

AC:

AN:

44696

Ashkenazi Jewish (ASJ)

AF:

0.0000383

AC:

AN:

26132

East Asian (EAS)

AF:

0.0000252

AC:

AN:

39692

South Asian (SAS)

AF:

0.00

AC:

AN:

86210

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53400

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

8.99e-7

AC:

AN:

1111784

Other (OTH)

AF:

0.00

AC:

AN:

60368

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.458

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

Alfa

AF:

0.00000384

Hom.:

128377

ExAC

AF:

0.00000828

AC:

EpiCase

AF:

0.00

EpiControl

AF:

0.0000593

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.095

BayesDel_addAF

Benign

-0.19

BayesDel_noAF

Benign

-0.34

CADD

Benign

(source)

DANN

Benign

0.93

DEOGEN2

Benign

0.036

Eigen

Benign

-1.2

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.10

LIST_S2

Benign

0.34

M_CAP

Benign

0.037

MetaRNN

Benign

0.14

MetaSVM

Uncertain

-0.057

MutationAssessor

Benign

0.0

PhyloP100

0.53

PrimateAI

Benign

0.33

PROVEAN

Uncertain

-2.9

REVEL

Benign

0.24

Sift

Uncertain

0.0090

Sift4G

Uncertain

0.032

Polyphen

0.0010

Vest4

0.26

MutPred

0.50

Gain of helix (P = 0.0425)

MVP

0.30

MPC

0.085

ClinPred

0.057

GERP RS

1.3

Varity_R

0.16

gMVP

0.38

Mutation Taster

=100/0

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over