dbSNP rs758077558: NOL4L:p.His550Arg (chr20-32452409-T-C) – 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.1649A>G(p.His550Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000687 in 1,455,972 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/19 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. H550P) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

NOL4L
NM_001256798.2 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.19

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:

ENSG00000236772 (HGNC:):

ENSG00000236772 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=0.12433249).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NOL4L	NM_001256798.2 link	c.1649A>G	p.His550Arg	missense_variant	Exon 10 of 11	ENST00000621426.7	NP_001243727.1	Q96MY1Q6P0R2A0A087X0N3
NOL4L	NM_080616.6 link	c.917A>G	p.His306Arg	missense_variant	Exon 7 of 8		NP_542183.2	Q96MY1-1
NOL4L	NM_001351680.2 link	c.917A>G	p.His306Arg	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.1649A>G	p.His550Arg	missense_variant	Exon 10 of 11	5	NM_001256798.2	ENSP00000483523.1	A0A087X0N3
ENSG00000236772	ENST00000442179.1 link	n.716+696T>C		intron_variant	Intron 3 of 3	1
NOL4L	ENST00000359676.9 link	c.917A>G	p.His306Arg	missense_variant	Exon 7 of 8	2		ENSP00000352704.5	Q96MY1-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.87e-7

AC:

AN:

1455972

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

724162

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33366

American (AMR)

AF:

0.00

AC:

AN:

44242

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25836

East Asian (EAS)

AF:

0.0000253

AC:

AN:

39454

South Asian (SAS)

AF:

0.00

AC:

AN:

85398

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52988

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5678

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1108878

Other (OTH)

AF:

0.00

AC:

AN:

60132

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.13

BayesDel_addAF

Benign

-0.11

BayesDel_noAF

Benign

-0.39

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.068

T;T;.

Eigen

Benign

-0.033

Eigen_PC

Benign

0.078

FATHMM_MKL

Uncertain

0.76

LIST_S2

Benign

0.85

D;D;D

M_CAP

Benign

0.0088

MetaRNN

Benign

0.12

T;T;T

MetaSVM

Benign

-1.1

PhyloP100

1.2

PROVEAN

Benign

-1.6

N;.;.

REVEL

Benign

0.039

Sift

Benign

0.34

T;.;.

Sift4G

Benign

0.47

T;T;T

Polyphen

0.76

P;.;.

Vest4

0.42

MutPred

0.16

Gain of phosphorylation at S307 (P = 0.0897);.;Gain of phosphorylation at S307 (P = 0.0897);

MVP

0.043

MPC

0.30

ClinPred

0.29

GERP RS

4.7

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.089

gMVP

0.19

Mutation Taster

=84/16

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

Computational scores

Splicing

Publications

Other links and lift over