NM_016167.5:c.9G>T

Variant names:

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_016167.5(NOL7):c.9G>T(p.Gln3His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000491 in 1,508,032 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 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. Q3R) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.000079 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000046 ( 0 hom. )

Consequence

NOL7
NM_016167.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.601

Publications

2 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:

SIRT5 (HGNC:14933): (sirtuin 5) This gene encodes a member of the sirtuin family of proteins, homologs to the yeast Sir2 protein. Members of the sirtuin family are characterized by a sirtuin core domain and grouped into four classes. The functions of human sirtuins have not yet been determined; however, yeast sirtuin proteins are known to regulate epigenetic gene silencing and suppress recombination of rDNA. Studies suggest that the human sirtuins may function as intracellular regulatory proteins with mono-ADP-ribosyltransferase activity. The protein encoded by this gene is included in class III of the sirtuin family. Alternative splicing of this gene results in multiple transcript variants. [provided by RefSeq, Jul 2010]

SIRT5 links:

ENSG00000261071 (HGNC:):

ENSG00000261071 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.01901719).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_016167.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
NOL7	NM_016167.5	MANE Select	c.9G>T	p.Gln3His	missense	Exon 1 of 8	NP_057251.2
NOL7	NM_001317724.2		c.9G>T	p.Gln3His	missense	Exon 1 of 9	NP_001304653.1	Q9UMY1-1
SIRT5	NM_012241.5	MANE Select	c.*3502G>T		downstream_gene	N/A	NP_036373.1	Q9NXA8-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
NOL7	ENST00000451315.7	TSL:1 MANE Select	c.9G>T	p.Gln3His	missense	Exon 1 of 8	ENSP00000405674.2	Q9UMY1-1
NOL7	ENST00000865196.1		c.9G>T	p.Gln3His	missense	Exon 1 of 9	ENSP00000535255.1
NOL7	ENST00000865197.1		c.9G>T	p.Gln3His	missense	Exon 1 of 6	ENSP00000535256.1

Frequencies

GnomAD3 genomes

AF:

0.0000788

AC:

AN:

152258

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000145

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000386

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.0000941

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000441

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000741

AC:

AN:

107914

AF XY:

0.0000707

show subpopulations

Gnomad AFR exome

AF:

0.000154

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000201

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000250

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000457

AC:

AN:

1355656

Hom.:

Cov.:

AF XY:

0.0000571

AC XY:

AN XY:

665366

show subpopulations

African (AFR)

AF:

0.0000652

AC:

AN:

30676

American (AMR)

AF:

0.00

AC:

AN:

31154

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

21700

East Asian (EAS)

AF:

0.000421

AC:

AN:

35600

South Asian (SAS)

AF:

0.000113

AC:

AN:

71098

European-Finnish (FIN)

AF:

0.0000238

AC:

AN:

42084

Middle Eastern (MID)

AF:

0.000254

AC:

AN:

3944

European-Non Finnish (NFE)

AF:

0.0000310

AC:

AN:

1063124

Other (OTH)

AF:

0.0000355

AC:

AN:

56276

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.495

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:

0.0000788

AC:

AN:

152376

Hom.:

Cov.:

AF XY:

0.0000403

AC XY:

AN XY:

74518

show subpopulations

African (AFR)

AF:

0.000144

AC:

AN:

41596

American (AMR)

AF:

0.00

AC:

AN:

15314

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.000387

AC:

AN:

5174

South Asian (SAS)

AF:

0.00

AC:

AN:

4834

European-Finnish (FIN)

AF:

0.0000941

AC:

AN:

10630

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0000441

AC:

AN:

68034

Other (OTH)

AF:

0.00

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

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:

0.0000831

ExAC

AF:

0.0000363

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.32

BayesDel_addAF

Benign

-0.38

BayesDel_noAF

Benign

-0.48

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.027

Eigen

Benign

-0.015

Eigen_PC

Benign

0.050

FATHMM_MKL

Uncertain

0.85

LIST_S2

Benign

0.72

M_CAP

Benign

0.014

MetaRNN

Benign

0.019

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.0

PhyloP100

0.60

PrimateAI

Uncertain

0.78

PROVEAN

Benign

-0.56

REVEL

Benign

0.037

Sift

Uncertain

0.013

Sift4G

Uncertain

0.045

Polyphen

0.61

Vest4

0.27

MutPred

0.20

Gain of methylation at R5 (P = 0.0488)

MVP

0.27

MPC

0.85

ClinPred

0.11

GERP RS

3.0

PromoterAI

-0.15

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

2.9

Varity_R

0.14

gMVP

0.13

Mutation Taster

=92/8

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over