Genetic Variant NOL4L:p.Ala618Val (chr20-32447786-G-A) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001256798.2(NOL4L):c.1853C>T(p.Ala618Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 12/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

NOL4L
NM_001256798.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.69

Publications

0 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:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.22425959).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NOL4L	NM_001256798.2 link	c.1853C>T	p.Ala618Val	missense_variant	Exon 11 of 11	ENST00000621426.7	NP_001243727.1	Q96MY1Q6P0R2A0A087X0N3
NOL4L	NM_080616.6 link	c.1121C>T	p.Ala374Val	missense_variant	Exon 8 of 8		NP_542183.2	Q96MY1-1
NOL4L	NM_001351680.2 link	c.*10C>T		3_prime_UTR_variant	Exon 9 of 9		NP_001338609.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NOL4L	ENST00000621426.7 link	c.1853C>T	p.Ala618Val	missense_variant	Exon 11 of 11	5	NM_001256798.2	ENSP00000483523.1		A0A087X0N3
NOL4L	ENST00000359676.9 link	c.1121C>T	p.Ala374Val	missense_variant	Exon 8 of 8	2		ENSP00000352704.5		Q96MY1-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1422212

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

701914

African (AFR)

AF:

0.00

AC:

AN:

32550

American (AMR)

AF:

0.00

AC:

AN:

41348

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

24156

East Asian (EAS)

AF:

0.00

AC:

AN:

39040

South Asian (SAS)

AF:

0.00

AC:

AN:

81384

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52324

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3992

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1088912

Other (OTH)

AF:

0.00

AC:

AN:

58506

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Jan 03, 2024

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The c.1121C>T (p.A374V) alteration is located in exon 8 (coding exon 7) of the NOL4L gene. This alteration results from a C to T substitution at nucleotide position 1121, causing the alanine (A) at amino acid position 374 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

0.079

BayesDel_addAF

Benign

-0.061

BayesDel_noAF

Benign

-0.33

CADD

Benign

(source)

DANN

Uncertain

0.97

DEOGEN2

Benign

0.068

T;T;.

Eigen

Uncertain

0.33

Eigen_PC

Uncertain

0.38

FATHMM_MKL

Uncertain

0.93

LIST_S2

Benign

0.73

T;T;T

M_CAP

Benign

0.0030

MetaRNN

Benign

0.22

T;T;T

MetaSVM

Benign

-0.90

PhyloP100

2.7

PROVEAN

Benign

-1.0

N;.;.

REVEL

Benign

0.11

Sift

Benign

0.14

T;.;.

Sift4G

Benign

0.14

T;T;D

Polyphen

0.96

D;.;.

Vest4

0.34

MutPred

0.12

Loss of relative solvent accessibility (P = 0.0071);.;Loss of relative solvent accessibility (P = 0.0071);

MVP

0.068

MPC

0.54

ClinPred

0.85

GERP RS

4.9

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.085

gMVP

0.46

Mutation Taster

=59/41

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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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over