20-32452395-C-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_001256798.2(NOL4L):c.1663G>A(p.Ala555Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000255 in 1,610,178 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.000026 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000025 ( 0 hom. )

Consequence

NOL4L
NM_001256798.2 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.308

Publications

1 publications found

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:

ENSG00000236772 (HGNC:):

ENSG00000236772 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.02351296).

BP6

Variant 20-32452395-C-T is Benign according to our data. Variant chr20-32452395-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 3920745.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High AC in GnomAdExome4 at 37 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NOL4L	NM_001256798.2 link	c.1663G>A	p.Ala555Thr	missense_variant	Exon 10 of 11	ENST00000621426.7	NP_001243727.1	Q96MY1Q6P0R2A0A087X0N3
NOL4L	NM_080616.6 link	c.931G>A	p.Ala311Thr	missense_variant	Exon 7 of 8		NP_542183.2	Q96MY1-1
NOL4L	NM_001351680.2 link	c.931G>A	p.Ala311Thr	missense_variant	Exon 7 of 9		NP_001338609.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
NOL4L	ENST00000621426.7 link	c.1663G>A	p.Ala555Thr	missense_variant	Exon 10 of 11	5	NM_001256798.2	ENSP00000483523.1	A0A087X0N3
ENSG00000236772	ENST00000442179.1 link	n.716+682C>T		intron_variant	Intron 3 of 3	1
NOL4L	ENST00000359676.9 link	c.931G>A	p.Ala311Thr	missense_variant	Exon 7 of 8	2		ENSP00000352704.5	Q96MY1-1

Frequencies

GnomAD3 genomes

AF:

0.0000263

AC:

AN:

152192

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000654

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000414

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000404

AC:

AN:

247558

AF XY:

0.0000449

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000147

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000110

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000254

AC:

AN:

1457986

Hom.:

Cov.:

AF XY:

0.0000317

AC XY:

AN XY:

725166

show subpopulations

African (AFR)

AF:

0.0000299

AC:

AN:

33396

American (AMR)

AF:

0.0000675

AC:

AN:

44444

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25944

East Asian (EAS)

AF:

0.000127

AC:

AN:

39498

South Asian (SAS)

AF:

0.000128

AC:

AN:

85730

European-Finnish (FIN)

AF:

0.0000188

AC:

AN:

53148

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5718

European-Non Finnish (NFE)

AF:

0.0000144

AC:

AN:

1109898

Other (OTH)

AF:

0.00

AC:

AN:

60210

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.468

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0000263

AC:

AN:

152192

Hom.:

Cov.:

AF XY:

0.0000404

AC XY:

AN XY:

74344

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41452

American (AMR)

AF:

0.0000654

AC:

AN:

15286

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5194

South Asian (SAS)

AF:

0.000414

AC:

AN:

4834

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10624

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.0000147

AC:

AN:

68014

Other (OTH)

AF:

0.00

AC:

AN:

2090

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.513

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.0000300

Hom.:

Bravo

AF:

0.0000491

ExAC

AF:

0.0000494

AC:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Mar 20, 2025

Ambry Genetics

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.058

BayesDel_addAF

Benign

-0.47

BayesDel_noAF

Benign

-0.66

CADD

Benign

8.8

(source)

DANN

Benign

0.90

DEOGEN2

Benign

0.032

T;T;.

Eigen

Benign

-1.4

Eigen_PC

Benign

-1.2

FATHMM_MKL

Benign

0.23

LIST_S2

Benign

0.70

T;T;T

M_CAP

Benign

0.0054

MetaRNN

Benign

0.024

T;T;T

MetaSVM

Benign

-0.98

PhyloP100

0.31

PROVEAN

Benign

-0.12

N;.;.

REVEL

Benign

0.097

Sift

Benign

0.74

T;.;.

Sift4G

Benign

0.66

T;T;T

Polyphen

0.0010

B;.;.

Vest4

0.24

MutPred

0.13

Gain of relative solvent accessibility (P = 0.0082);.;Gain of relative solvent accessibility (P = 0.0082);

MVP

0.043

MPC

0.23

ClinPred

0.010

GERP RS

-0.66

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.016

gMVP

0.20

Mutation Taster

=100/0

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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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20-32452395-C-T

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over