Variant 20-32453754-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_001256798.2(NOL4L):c.1127C>G(p.Pro376Arg) variant causes a missense change. The variant allele was found at a frequency of 0.0000618 in 1,552,928 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00012 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000055 ( 1 hom. )

Consequence

NOL4L
NM_001256798.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.21

Variant links:

Genes affected

NOL4L (HGNC:16106): (nucleolar protein 4 like) Located in cytosol and nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

NOL4L links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.055582613).

BS2

High AC in GnomAd4 at 19 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NOL4L	NM_001256798.2 linkuse as main transcript	c.1127C>G	p.Pro376Arg	missense_variant	7/11	ENST00000621426.7	NP_001243727.1	Q96MY1Q6P0R2A0A087X0N3
NOL4L	NM_080616.6 linkuse as main transcript	c.395C>G	p.Pro132Arg	missense_variant	4/8		NP_542183.2	Q96MY1-1
NOL4L	NM_001351680.2 linkuse as main transcript	c.395C>G	p.Pro132Arg	missense_variant	4/9		NP_001338609.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
NOL4L	ENST00000621426.7 linkuse as main transcript	c.1127C>G	p.Pro376Arg	missense_variant	7/11	5	NM_001256798.2	ENSP00000483523.1	A0A087X0N3
NOL4L	ENST00000359676.9 linkuse as main transcript	c.395C>G	p.Pro132Arg	missense_variant	4/8	2		ENSP00000352704.5	Q96MY1-1
NOL4L	ENST00000475781.1 linkuse as main transcript	n.465C>G		non_coding_transcript_exon_variant	5/7	5		ENSP00000492149.1	A0A1W2PQU1

Frequencies

GnomAD3 genomes

AF:

0.000125

AC:

AN:

152128

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000483

Gnomad AMI

AF:

0.00768

Gnomad AMR

AF:

0.0000654

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.0000943

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000118

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000838

AC:

AN:

155084

Hom.:

AF XY:

0.0000978

AC XY:

AN XY:

81810

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000863

Gnomad SAS exome

AF:

0.000175

Gnomad FIN exome

AF:

0.0000655

Gnomad NFE exome

AF:

0.000119

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000550

AC:

AN:

1400684

Hom.:

Cov.:

AF XY:

0.0000593

AC XY:

AN XY:

690960

show subpopulations

Gnomad4 AFR exome

AF:

0.0000315

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.0000397

Gnomad4 EAS exome

AF:

0.0000278

Gnomad4 SAS exome

AF:

0.0000630

Gnomad4 FIN exome

AF:

0.000122

Gnomad4 NFE exome

AF:

0.0000574

Gnomad4 OTH exome

AF:

0.0000172

GnomAD4 genome

AF:

0.000125

AC:

AN:

152244

Hom.:

Cov.:

AF XY:

0.000108

AC XY:

AN XY:

74418

show subpopulations

Gnomad4 AFR

AF:

0.0000482

Gnomad4 AMR

AF:

0.0000654

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.0000943

Gnomad4 NFE

AF:

0.000118

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000203

Hom.:

Bravo

AF:

0.000155

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

Sep 23, 2023

The c.395C>G (p.P132R) alteration is located in exon 4 (coding exon 3) of the NOL4L gene. This alteration results from a C to G substitution at nucleotide position 395, causing the proline (P) at amino acid position 132 to be replaced by an arginine (R). 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

Uncertain

0.37

BayesDel_addAF

Benign

-0.19

BayesDel_noAF

Benign

-0.25

CADD

Uncertain

DANN

Benign

0.63

DEOGEN2

Benign

0.044

T;T;.

Eigen

Uncertain

0.19

Eigen_PC

Benign

0.22

FATHMM_MKL

Uncertain

0.97

LIST_S2

Uncertain

0.94

D;D;D

M_CAP

Benign

0.0048

MetaRNN

Benign

0.056

T;T;T

MetaSVM

Benign

-0.90

PROVEAN

Benign

-0.36

N;.;.

REVEL

Benign

0.089

Sift

Benign

0.036

D;.;.

Sift4G

Benign

0.42

T;T;T

Polyphen

0.93

P;.;.

Vest4

0.49

MutPred

0.22

Loss of catalytic residue at P131 (P = 0.0168);.;Loss of catalytic residue at P131 (P = 0.0168);

MVP

0.043

MPC

0.42

ClinPred

0.11

GERP RS

5.0

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.060

gMVP

0.16

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