6-13615419-G-C

Variant names:

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>C(p.Glu21Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000518 in 1,545,782 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0000043 ( 0 hom. )

Consequence

NOL7
NM_016167.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

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:

Genome browser will be placed here

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=0.09963697).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NOL7	NM_016167.5 link	c.61G>C	p.Glu21Gln	missense_variant	Exon 1 of 8	ENST00000451315.7	NP_057251.2	Q9UMY1-1A0A024QZW2
NOL7	NM_001317724.2 link	c.61G>C	p.Glu21Gln	missense_variant	Exon 1 of 9		NP_001304653.1	Q9UMY1-1A0A024QZW2
LOC124901263	XR_007059461.1 link	n.-217C>G		upstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
NOL7	ENST00000451315.7 link	c.61G>C	p.Glu21Gln	missense_variant	Exon 1 of 8	1	NM_016167.5	ENSP00000405674.2	Q9UMY1-1
NOL7	ENST00000420088.1 link	c.-129G>C		upstream_gene_variant		2		ENSP00000404836.1	H7C2B1
NOL7	ENST00000474485.1 link	n.-170G>C		upstream_gene_variant		3
ENSG00000261071	ENST00000566170.3 link	n.-206C>G		upstream_gene_variant		6

Frequencies

GnomAD3 genomes

AF:

0.0000131

AC:

AN:

152258

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:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000294

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.00000431

AC:

AN:

1393524

Hom.:

Cov.:

AF XY:

0.00000146

AC XY:

AN XY:

687018

show subpopulations

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:

0.00000557

AC:

AN:

1077346

Other (OTH)

AF:

0.00

AC:

AN:

57694

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.483

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0000131

AC:

AN:

152258

Hom.:

Cov.:

AF XY:

0.0000134

AC XY:

AN XY:

74390

show subpopulations

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.00

AC:

AN:

41480

American (AMR)

AF:

0.00

AC:

AN:

15292

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3468

East Asian (EAS)

AF:

0.00

AC:

AN:

5200

South Asian (SAS)

AF:

0.00

AC:

AN:

4834

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10632

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.0000294

AC:

AN:

68034

Other (OTH)

AF:

0.00

AC:

AN:

2090

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0.029673), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.400

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.0000151

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Apr 03, 2025

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The c.61G>C (p.E21Q) alteration is located in exon 1 (coding exon 1) of the NOL7 gene. This alteration results from a G to C substitution at nucleotide position 61, causing the glutamic acid (E) at amino acid position 21 to be replaced by a glutamine (Q). 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

0.18

BayesDel_addAF

Benign

-0.26

BayesDel_noAF

Benign

-0.61

CADD

Uncertain

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.015

Eigen

Benign

-0.16

Eigen_PC

Benign

-0.026

FATHMM_MKL

Uncertain

0.85

LIST_S2

Benign

0.78

M_CAP

Benign

0.018

MetaRNN

Benign

0.10

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.69

PhyloP100

0.97

PrimateAI

Pathogenic

0.88

PROVEAN

Benign

-0.38

REVEL

Benign

0.091

Sift

Benign

0.19

Sift4G

Benign

0.31

Polyphen

0.29

Vest4

0.25

MutPred

0.054

Gain of MoRF binding (P = 0.0948);

MVP

0.22

MPC

0.93

ClinPred

0.66

GERP RS

2.9

PromoterAI

-0.068

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.18

gMVP

0.13

Mutation Taster

=94/6

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

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over