Genetic Variant NOL7:p.Glu21Lys (chr6-13615419-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_016167.5(NOL7):c.61G>A(p.Glu21Lys) 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. 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. E21Q) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

NOL7
NM_016167.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.966

Publications

0 publications found

Variant links:

Genes affected

NOL7 (HGNC:21040): (nucleolar protein 7) The protein encoded by this gene localizes to the nucleolus, where it maintains nucleolar structure and cell growth rates. The encoded protein also functions as a tumor suppressor and regulator of angiogenesis. The RB tumor suppressor gene recruits transcription factors to this gene and positively regulates its expression. Two transcript variants encoding the same protein have been found for this gene. [provided by RefSeq, Dec 2015]

NOL7 links:

ENSG00000261071 (HGNC:):

ENSG00000261071 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=0.17798531).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NOL7	NM_016167.5 link	c.61G>A	p.Glu21Lys	missense_variant	Exon 1 of 8	ENST00000451315.7	NP_057251.2	Q9UMY1-1A0A024QZW2
NOL7	NM_001317724.2 link	c.61G>A	p.Glu21Lys	missense_variant	Exon 1 of 9		NP_001304653.1	Q9UMY1-1A0A024QZW2
LOC124901263	XR_007059461.1 link	n.-217C>T		upstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
NOL7	ENST00000451315.7 link	c.61G>A	p.Glu21Lys	missense_variant	Exon 1 of 8	1	NM_016167.5	ENSP00000405674.2	Q9UMY1-1
NOL7	ENST00000420088.1 link	c.-129G>A		upstream_gene_variant		2		ENSP00000404836.1	H7C2B1
NOL7	ENST00000474485.1 link	n.-170G>A		upstream_gene_variant		3
ENSG00000261071	ENST00000566170.3 link	n.-206C>T		upstream_gene_variant		6

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1393524

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

687018

African (AFR)

AF:

0.00

AC:

AN:

31386

American (AMR)

AF:

0.00

AC:

AN:

35026

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

24968

East Asian (EAS)

AF:

0.00

AC:

AN:

35670

South Asian (SAS)

AF:

0.00

AC:

AN:

78916

European-Finnish (FIN)

AF:

0.00

AC:

AN:

47738

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4780

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1077346

Other (OTH)

AF:

0.00

AC:

AN:

57694

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.17

BayesDel_addAF

Benign

-0.16

BayesDel_noAF

Benign

-0.47

CADD

Pathogenic

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.023

Eigen

Benign

0.13

Eigen_PC

Benign

0.18

FATHMM_MKL

Uncertain

0.85

LIST_S2

Benign

0.84

M_CAP

Uncertain

0.11

MetaRNN

Benign

0.18

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.0

PhyloP100

0.97

PrimateAI

Pathogenic

0.92

PROVEAN

Benign

-0.69

REVEL

Benign

0.057

Sift

Uncertain

0.013

Sift4G

Benign

0.10

Polyphen

0.92

Vest4

0.40

MutPred

0.11

Gain of ubiquitination at E21 (P = 0.0029);

MVP

0.16

MPC

0.84

ClinPred

0.64

GERP RS

2.9

PromoterAI

0.021

Neutral

(source)

Varity_R

0.29

gMVP

0.19

Mutation Taster

=91/9

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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