Genetic Variant NOL4:p.Arg371Gln (chr18-33958363-C-T) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 2P and 6B. PM2BP4_ModerateBS2

The NM_003787.5(NOL4):c.1112G>A(p.Arg371Gln) variant causes a missense change. The variant allele was found at a frequency of 0.00000355 in 1,406,620 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000036 ( 0 hom. )

Consequence

NOL4
NM_003787.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.77

Publications

5 publications found

Variant links:

Genes affected

NOL4 (HGNC:7870): (nucleolar protein 4) Predicted to enable RNA binding activity. Predicted to be located in nucleolus. [provided by Alliance of Genome Resources, Apr 2022]

NOL4 links:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.15015924).

BS2

High AC in GnomAdExome4 at 5 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003787.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
NOL4	NM_003787.5	MANE Select	c.1112G>A	p.Arg371Gln	missense	Exon 7 of 11	NP_003778.2	O94818-1
NOL4	NM_001384467.1		c.1181G>A	p.Arg394Gln	missense	Exon 8 of 12	NP_001371396.1
NOL4	NM_001384468.1		c.1181G>A	p.Arg394Gln	missense	Exon 8 of 11	NP_001371397.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
NOL4	ENST00000261592.10	TSL:1 MANE Select	c.1112G>A	p.Arg371Gln	missense	Exon 7 of 11	ENSP00000261592.4	O94818-1
NOL4	ENST00000589544.5	TSL:1	c.1112G>A	p.Arg371Gln	missense	Exon 7 of 9	ENSP00000465450.1	O94818-2
NOL4	ENST00000538587.5	TSL:2	c.890G>A	p.Arg297Gln	missense	Exon 7 of 11	ENSP00000443472.1	O94818-3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000811

AC:

AN:

246480

AF XY:

0.0000150

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000298

Gnomad ASJ exome

AF:

0.00

Gnomad EAS 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:

0.00000355

AC:

AN:

1406620

Hom.:

Cov.:

AF XY:

0.00000429

AC XY:

AN XY:

698640

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

32062

American (AMR)

AF:

0.0000239

AC:

AN:

41794

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

24706

East Asian (EAS)

AF:

0.0000266

AC:

AN:

37584

South Asian (SAS)

AF:

0.0000131

AC:

AN:

76062

European-Finnish (FIN)

AF:

0.00

AC:

AN:

50900

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5518

European-Non Finnish (NFE)

AF:

0.00000185

AC:

AN:

1080490

Other (OTH)

AF:

0.00

AC:

AN:

57504

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.465

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:

0.00

Hom.:

ExAC

AF:

0.00000824

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.090

BayesDel_addAF

Uncertain

0.029

BayesDel_noAF

Benign

-0.20

CADD

Uncertain

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.024

Eigen

Uncertain

0.22

Eigen_PC

Uncertain

0.25

FATHMM_MKL

Uncertain

0.79

LIST_S2

Uncertain

0.96

M_CAP

Uncertain

0.11

MetaRNN

Benign

0.15

MetaSVM

Uncertain

-0.25

MutationAssessor

Uncertain

2.2

PhyloP100

3.8

PrimateAI

Benign

0.38

PROVEAN

Benign

-0.47

REVEL

Benign

0.25

Sift

Benign

0.18

Sift4G

Benign

0.58

Polyphen

0.98

Vest4

0.38

MutPred

0.23

Gain of relative solvent accessibility (P = 0.1571)

MVP

0.50

MPC

0.22

ClinPred

0.32

GERP RS

5.6

Varity_R

0.11

gMVP

0.39

Mutation Taster

=88/12

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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