Variant 20-32447727-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_001256798.2(NOL4L):c.1912G>A(p.Val638Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000141 in 1,346,792 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.000014 ( 0 hom., cov: 31)

Exomes 𝑓: 0.000014 ( 0 hom. )

Consequence

NOL4L
NM_001256798.2 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.16

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 -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.031833082).

BP6

Variant 20-32447727-C-T is Benign according to our data. Variant chr20-32447727-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 3201062.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High AC in GnomAdExome4 at 17 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NOL4L	NM_001256798.2 linkuse as main transcript	c.1912G>A	p.Val638Met	missense_variant	11/11	ENST00000621426.7	NP_001243727.1	Q96MY1Q6P0R2A0A087X0N3
NOL4L	NM_080616.6 linkuse as main transcript	c.1180G>A	p.Val394Met	missense_variant	8/8		NP_542183.2	Q96MY1-1
NOL4L	NM_001351680.2 linkuse as main transcript	c.*69G>A		3_prime_UTR_variant	9/9		NP_001338609.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NOL4L	ENST00000621426.7 linkuse as main transcript	c.1912G>A	p.Val638Met	missense_variant	11/11	5	NM_001256798.2	ENSP00000483523.1		A0A087X0N3
NOL4L	ENST00000359676.9 linkuse as main transcript	c.1180G>A	p.Val394Met	missense_variant	8/8	2		ENSP00000352704.5		Q96MY1-1

Frequencies

GnomAD3 genomes

AF:

0.0000143

AC:

AN:

139718

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000260

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000154

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000164

AC:

AN:

243652

Hom.:

AF XY:

0.0000151

AC XY:

AN XY:

132482

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000299

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000996

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000141

AC:

AN:

1207074

Hom.:

Cov.:

AF XY:

0.0000134

AC XY:

AN XY:

597492

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000540

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000850

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000849

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000143

AC:

AN:

139718

Hom.:

Cov.:

AF XY:

0.0000147

AC XY:

AN XY:

67820

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000260

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000154

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000301

Hom.:

Bravo

AF:

0.0000113

ExAC

AF:

0.0000165

AC:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Oct 13, 2023

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.069

BayesDel_addAF

Benign

-0.38

BayesDel_noAF

Benign

-0.58

CADD

Benign

DANN

Benign

0.91

DEOGEN2

Benign

0.025

T;T

Eigen

Benign

-0.89

Eigen_PC

Benign

-0.65

FATHMM_MKL

Benign

0.49

LIST_S2

Benign

0.81

T;T

M_CAP

Benign

0.0018

MetaRNN

Benign

0.032

T;T

MetaSVM

Benign

-1.1

PROVEAN

Benign

0.35

N;.

REVEL

Benign

0.052

Sift

Benign

1.0

T;.

Sift4G

Benign

0.48

T;T

Polyphen

0.0

B;.

Vest4

0.14

MutPred

0.11

Loss of phosphorylation at T396 (P = 0.0749);.;

MVP

0.043

MPC

0.24

ClinPred

0.022

GERP RS

2.6

Varity_R

0.025

gMVP

0.16

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