Variant 20-32456149-C-T 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_001256798.2(NOL4L):c.1088G>A(p.Arg363His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000282 in 1,559,724 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 11/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000030 ( 0 hom. )

Consequence

NOL4L
NM_001256798.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.32

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 Likely_benign. Variant got -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.17361927).

BS2

High AC in GnomAdExome4 at 42 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NOL4L	NM_001256798.2 linkuse as main transcript	c.1088G>A	p.Arg363His	missense_variant	6/11	ENST00000621426.7	NP_001243727.1	Q96MY1Q6P0R2A0A087X0N3
NOL4L	NM_080616.6 linkuse as main transcript	c.356G>A	p.Arg119His	missense_variant	3/8		NP_542183.2	Q96MY1-1
NOL4L	NM_001351680.2 linkuse as main transcript	c.356G>A	p.Arg119His	missense_variant	3/9		NP_001338609.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
NOL4L	ENST00000621426.7 linkuse as main transcript	c.1088G>A	p.Arg363His	missense_variant	6/11	5	NM_001256798.2	ENSP00000483523.1	A0A087X0N3
NOL4L	ENST00000359676.9 linkuse as main transcript	c.356G>A	p.Arg119His	missense_variant	3/8	2		ENSP00000352704.5	Q96MY1-1
NOL4L	ENST00000475781.1 linkuse as main transcript	n.356G>A		non_coding_transcript_exon_variant	3/7	5		ENSP00000492149.1	A0A1W2PQU1

Frequencies

GnomAD3 genomes

AF:

0.0000131

AC:

AN:

152256

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:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000294

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000620

AC:

AN:

209644

Hom.:

AF XY:

0.0000707

AC XY:

AN XY:

113142

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000712

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000206

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000298

AC:

AN:

1407350

Hom.:

Cov.:

AF XY:

0.0000331

AC XY:

AN XY:

695062

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000263

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000750

Gnomad4 SAS exome

AF:

0.0000127

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000923

Gnomad4 OTH exome

AF:

0.0000172

GnomAD4 genome

AF:

0.0000131

AC:

AN:

152374

Hom.:

Cov.:

AF XY:

0.0000134

AC XY:

AN XY:

74514

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000294

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000151

ExAC

AF:

0.0000578

AC:

Asia WGS

AF:

0.000866

AC:

AN:

3478

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 29, 2022

The c.356G>A (p.R119H) alteration is located in exon 3 (coding exon 2) of the NOL4L gene. This alteration results from a G to A substitution at nucleotide position 356, causing the arginine (R) at amino acid position 119 to be replaced by a histidine (H). 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

0.22

BayesDel_addAF

Benign

-0.40

BayesDel_noAF

Benign

-0.43

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.056

T;T;.

Eigen

Benign

-0.018

Eigen_PC

Benign

0.11

FATHMM_MKL

Uncertain

0.93

LIST_S2

Uncertain

0.86

D;D;D

M_CAP

Benign

0.0096

MetaRNN

Benign

0.17

T;T;T

MetaSVM

Benign

-0.76

PROVEAN

Benign

-0.63

N;.;.

REVEL

Benign

0.040

Sift

Benign

0.18

T;.;.

Sift4G

Benign

0.074

T;T;T

Polyphen

0.077

B;.;.

Vest4

0.67

MutPred

0.38

Gain of helix (P = 0.0325);.;Gain of helix (P = 0.0325);

MVP

0.043

MPC

1.0

ClinPred

0.17

GERP RS

4.1

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.042

gMVP

0.22

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.040

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