Variant 20-32452996-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP4BS2

The NM_001256798.2(NOL4L):c.1508C>T(p.Thr503Met) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000143 in 1,613,376 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: 𝑓 0.0000066 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000015 ( 0 hom. )

Consequence

NOL4L
NM_001256798.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.77

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:

(HGNC:):

links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -5 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.35857093).

BS2

High AC in GnomAdExome at 9 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
NOL4L	NM_001256798.2 linkuse as main transcript	c.1508C>T	p.Thr503Met	missense_variant	9/11	ENST00000621426.7
NOL4L	NM_080616.6 linkuse as main transcript	c.776C>T	p.Thr259Met	missense_variant	6/8
NOL4L	NM_001351680.2 linkuse as main transcript	c.776C>T	p.Thr259Met	missense_variant	6/9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NOL4L	ENST00000621426.7 linkuse as main transcript	c.1508C>T	p.Thr503Met	missense_variant	9/11	5	NM_001256798.2	P1
	ENST00000442179.1 linkuse as main transcript	n.717-342G>A		intron_variant, non_coding_transcript_variant		1
NOL4L	ENST00000359676.9 linkuse as main transcript	c.776C>T	p.Thr259Met	missense_variant	6/8	2			Q96MY1-1
NOL4L	ENST00000475781.1 linkuse as main transcript	c.*327C>T		3_prime_UTR_variant, NMD_transcript_variant	7/7	5

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152224

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000359

AC:

AN:

250778

Hom.:

AF XY:

0.0000221

AC XY:

AN XY:

135602

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000578

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000327

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000528

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000151

AC:

AN:

1461152

Hom.:

Cov.:

AF XY:

0.0000138

AC XY:

AN XY:

726912

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000224

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000464

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000989

Gnomad4 OTH exome

AF:

0.0000994

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152224

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74382

show subpopulations

Gnomad4 AFR

AF:

0.0000241

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:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000113

ExAC

AF:

0.0000165

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

Oct 26, 2022

The c.776C>T (p.T259M) alteration is located in exon 6 (coding exon 5) of the NOL4L gene. This alteration results from a C to T substitution at nucleotide position 776, causing the threonine (T) at amino acid position 259 to be replaced by a methionine (M). 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

Pathogenic

0.80

BayesDel_addAF

Uncertain

0.054

BayesDel_noAF

Uncertain

0.020

Cadd

Pathogenic

Dann

Uncertain

1.0

DEOGEN2

Benign

0.29

T;T;.

Eigen

Uncertain

0.55

Eigen_PC

Uncertain

0.50

FATHMM_MKL

Pathogenic

0.97

LIST_S2

Uncertain

0.96

D;D;D

M_CAP

Benign

0.0084

MetaRNN

Benign

0.36

T;T;T

MetaSVM

Benign

-0.60

MutationTaster

Benign

1.0

PROVEAN

Pathogenic

-4.4

D;.;.

REVEL

Uncertain

0.30

Sift

Benign

0.045

D;.;.

Sift4G

Uncertain

0.060

T;T;T

Polyphen

1.0

D;.;.

Vest4

0.68

MutPred

0.19

Loss of glycosylation at T259 (P = 0.0126);.;Loss of glycosylation at T259 (P = 0.0126);

MVP

0.21

MPC

1.9

ClinPred

0.47

GERP RS

3.5

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.9

Varity_R

0.16

gMVP

0.61

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

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