Variant 20-32447768-G-A 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.1871C>T(p.Thr624Ile) variant causes a missense change. The variant allele was found at a frequency of 0.0000259 in 1,586,034 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 (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. T624N) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.000026 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000026 ( 0 hom. )

Consequence

NOL4L
NM_001256798.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.17

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=0.10073435).

BS2

High AC in GnomAdExome at 10 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
NOL4L	NM_001256798.2 linkuse as main transcript	c.1871C>T	p.Thr624Ile	missense_variant	11/11	ENST00000621426.7
NOL4L	NM_080616.6 linkuse as main transcript	c.1139C>T	p.Thr380Ile	missense_variant	8/8
NOL4L	NM_001351680.2 linkuse as main transcript	c.*28C>T		3_prime_UTR_variant	9/9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NOL4L	ENST00000621426.7 linkuse as main transcript	c.1871C>T	p.Thr624Ile	missense_variant	11/11	5	NM_001256798.2	P1
NOL4L	ENST00000359676.9 linkuse as main transcript	c.1139C>T	p.Thr380Ile	missense_variant	8/8	2			Q96MY1-1

Frequencies

GnomAD3 genomes

AF:

0.0000263

AC:

AN:

152178

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

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:

0.0000147

Gnomad OTH

AF:

0.000479

GnomAD3 exomes

AF:

0.0000427

AC:

AN:

234358

Hom.:

AF XY:

0.0000394

AC XY:

AN XY:

126786

show subpopulations

Gnomad AFR exome

AF:

0.0000645

Gnomad AMR exome

AF:

0.000183

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000190

Gnomad OTH exome

AF:

0.000176

GnomAD4 exome

AF:

0.0000258

AC:

AN:

1433856

Hom.:

Cov.:

AF XY:

0.0000183

AC XY:

AN XY:

708962

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000187

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000256

Gnomad4 OTH exome

AF:

0.0000170

GnomAD4 genome

AF:

0.0000263

AC:

AN:

152178

Hom.:

Cov.:

AF XY:

0.0000404

AC XY:

AN XY:

74346

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.000131

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.000479

Alfa

AF:

0.0000553

Hom.:

Bravo

AF:

0.0000642

ExAC

AF:

0.0000330

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

Apr 12, 2022

The c.1139C>T (p.T380I) 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 1139, causing the threonine (T) at amino acid position 380 to be replaced by an isoleucine (I). 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

0.10

BayesDel_addAF

Benign

-0.32

BayesDel_noAF

Benign

-0.43

Cadd

Uncertain

Dann

Benign

0.96

DEOGEN2

Benign

0.058

T;T;.

Eigen

Benign

-0.37

Eigen_PC

Benign

-0.23

FATHMM_MKL

Uncertain

0.93

LIST_S2

Benign

0.73

T;T;T

M_CAP

Benign

0.0084

MetaRNN

Benign

0.10

T;T;T

MetaSVM

Benign

-1.0

MutationTaster

Benign

0.98

PROVEAN

Benign

-1.2

N;.;.

REVEL

Benign

0.063

Sift

Benign

0.093

T;.;.

Sift4G

Benign

0.30

T;T;T

Polyphen

0.23

B;.;.

Vest4

0.20

MutPred

0.16

Loss of glycosylation at T380 (P = 9e-04);.;Loss of glycosylation at T380 (P = 9e-04);

MVP

0.043

MPC

0.85

ClinPred

0.053

GERP RS

3.9

Varity_R

0.054

gMVP

0.37

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

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