Variant 20-32453754-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_001256798.2(NOL4L):c.1127C>A(p.Pro376His) variant causes a missense change. The variant allele was found at a frequency of 0.000194 in 1,552,926 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00017 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00020 ( 1 hom. )

Consequence

NOL4L
NM_001256798.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.21

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 Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.035380423).

BS2

High AC in GnomAd4 at 26 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NOL4L	NM_001256798.2 linkuse as main transcript	c.1127C>A	p.Pro376His	missense_variant	7/11	ENST00000621426.7	NP_001243727.1	Q96MY1Q6P0R2A0A087X0N3
NOL4L	NM_080616.6 linkuse as main transcript	c.395C>A	p.Pro132His	missense_variant	4/8		NP_542183.2	Q96MY1-1
NOL4L	NM_001351680.2 linkuse as main transcript	c.395C>A	p.Pro132His	missense_variant	4/9		NP_001338609.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
NOL4L	ENST00000621426.7 linkuse as main transcript	c.1127C>A	p.Pro376His	missense_variant	7/11	5	NM_001256798.2	ENSP00000483523.1	A0A087X0N3
NOL4L	ENST00000359676.9 linkuse as main transcript	c.395C>A	p.Pro132His	missense_variant	4/8	2		ENSP00000352704.5	Q96MY1-1
NOL4L	ENST00000475781.1 linkuse as main transcript	n.465C>A		non_coding_transcript_exon_variant	5/7	5		ENSP00000492149.1	A0A1W2PQU1

Frequencies

GnomAD3 genomes

AF:

0.000171

AC:

AN:

152128

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000966

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000196

Gnomad ASJ

AF:

0.000865

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000414

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000206

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000213

AC:

AN:

155084

Hom.:

AF XY:

0.000122

AC XY:

AN XY:

81810

show subpopulations

Gnomad AFR exome

AF:

0.000225

Gnomad AMR exome

AF:

0.000524

Gnomad ASJ exome

AF:

0.000117

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000131

Gnomad FIN exome

AF:

0.0000655

Gnomad NFE exome

AF:

0.000221

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000197

AC:

276

AN:

1400682

Hom.:

Cov.:

AF XY:

0.000185

AC XY:

128

AN XY:

690958

show subpopulations

Gnomad4 AFR exome

AF:

0.000315

Gnomad4 AMR exome

AF:

0.000448

Gnomad4 ASJ exome

AF:

0.000318

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000214

Gnomad4 FIN exome

AF:

0.0000608

Gnomad4 NFE exome

AF:

0.000195

Gnomad4 OTH exome

AF:

0.000103

GnomAD4 genome

AF:

0.000171

AC:

AN:

152244

Hom.:

Cov.:

AF XY:

0.000228

AC XY:

AN XY:

74418

show subpopulations

Gnomad4 AFR

AF:

0.0000963

Gnomad4 AMR

AF:

0.000196

Gnomad4 ASJ

AF:

0.000865

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000415

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000206

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000163

Hom.:

Bravo

AF:

0.000174

ExAC

AF:

0.0000815

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

Sep 14, 2021

The c.395C>A (p.P132H) alteration is located in exon 4 (coding exon 3) of the NOL4L gene. This alteration results from a C to A substitution at nucleotide position 395, causing the proline (P) at amino acid position 132 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

0.30

BayesDel_addAF

Benign

-0.25

BayesDel_noAF

Benign

-0.24

CADD

Uncertain

DANN

Uncertain

0.99

DEOGEN2

Benign

0.063

T;T;.

Eigen

Uncertain

0.42

Eigen_PC

Uncertain

0.39

FATHMM_MKL

Uncertain

0.94

LIST_S2

Benign

0.84

T;D;T

M_CAP

Benign

0.0088

MetaRNN

Benign

0.035

T;T;T

MetaSVM

Benign

-0.45

PROVEAN

Benign

-1.2

N;.;.

REVEL

Benign

0.13

Sift

Uncertain

0.0090

D;.;.

Sift4G

Uncertain

0.040

D;T;D

Polyphen

0.99

D;.;.

Vest4

0.47

MVP

0.068

MPC

0.81

ClinPred

0.062

GERP RS

5.0

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.097

gMVP

0.17

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

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