Variant chr18-34223030-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_003787.5(NOL4):c.224G>T(p.Gly75Val) variant causes a missense change. The variant allele was found at a frequency of 0.00000992 in 1,612,720 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G75C) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000010 ( 0 hom. )

Consequence

NOL4
NM_003787.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.80

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:

(HGNC:):

links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.13258493).

BS2

High AC in GnomAdExome4 at 15 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NOL4	NM_003787.5 linkuse as main transcript	c.224G>T	p.Gly75Val	missense_variant	1/11	ENST00000261592.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NOL4	ENST00000261592.10 linkuse as main transcript	c.224G>T	p.Gly75Val	missense_variant	1/11	1	NM_003787.5	P1	O94818-1
NOL4	ENST00000589544.5 linkuse as main transcript	c.224G>T	p.Gly75Val	missense_variant	1/9	1			O94818-2
	ENST00000587528.1 linkuse as main transcript	n.66C>A		non_coding_transcript_exon_variant	1/2	3
NOL4	ENST00000590712.5 linkuse as main transcript	c.176G>T	p.Gly59Val	missense_variant	1/10	2

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152222

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:

0.000193

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000363

AC:

AN:

248036

Hom.:

AF XY:

0.0000445

AC XY:

AN XY:

134764

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000501

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:

0.0000103

AC:

AN:

1460498

Hom.:

Cov.:

AF XY:

0.0000110

AC XY:

AN XY:

726640

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000353

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:

0.00000657

AC:

AN:

152222

Hom.:

Cov.:

AF XY:

0.0000134

AC XY:

AN XY:

74366

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000227

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

May 03, 2023

The c.224G>T (p.G75V) alteration is located in exon 1 (coding exon 1) of the NOL4 gene. This alteration results from a G to T substitution at nucleotide position 224, causing the glycine (G) at amino acid position 75 to be replaced by a valine (V). 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

0.082

BayesDel_addAF

Benign

-0.19

BayesDel_noAF

Benign

-0.18

CADD

Pathogenic

DANN

Uncertain

0.98

DEOGEN2

Benign

0.036

T;.;T

Eigen

Benign

-0.0045

Eigen_PC

Benign

0.20

FATHMM_MKL

Benign

0.72

LIST_S2

Uncertain

0.87

D;D;D

M_CAP

Benign

0.079

MetaRNN

Benign

0.13

T;T;T

MetaSVM

Benign

-0.44

MutationAssessor

Benign

0.69

N;N;.

MutationTaster

Benign

1.0

D;D;D

PrimateAI

Uncertain

0.57

PROVEAN

Benign

-1.1

N;.;.

REVEL

Benign

0.27

Sift

Benign

0.11

T;.;.

Sift4G

Benign

0.14

T;T;T

Polyphen

0.0090

B;B;.

Vest4

0.32

MutPred

0.36

Loss of disorder (P = 0.0378);Loss of disorder (P = 0.0378);.;

MVP

0.17

MPC

1.4

ClinPred

0.076

GERP RS

5.7

Varity_R

0.22

gMVP

0.67

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