6-13615381-C-A

Variant names:

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_016167.5(NOL7):c.23C>A(p.Ala8Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000573 in 1,517,980 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000020 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000062 ( 0 hom. )

Consequence

NOL7
NM_016167.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.33

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 made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.029808432).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NOL7	NM_016167.5 link	c.23C>A	p.Ala8Glu	missense_variant	Exon 1 of 8	ENST00000451315.7	NP_057251.2	Q9UMY1-1A0A024QZW2
SIRT5	NM_012241.5 link	c.*3516C>A		downstream_gene_variant		ENST00000606117.2	NP_036373.1	Q9NXA8-1A0A024R012

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NOL7	ENST00000451315.7 link	c.23C>A	p.Ala8Glu	missense_variant	Exon 1 of 8	1	NM_016167.5	ENSP00000405674.2		Q9UMY1-1
SIRT5	ENST00000606117.2 link	c.*3516C>A		downstream_gene_variant		1	NM_012241.5	ENSP00000476228.1		Q9NXA8-1

Frequencies

GnomAD3 genomes

AF:

0.0000197

AC:

AN:

152256

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

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

GnomAD3 exomes

AF:

0.0000256

AC:

AN:

117274

Hom.:

AF XY:

0.0000322

AC XY:

AN XY:

62194

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

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:

0.0000689

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000615

AC:

AN:

1365724

Hom.:

Cov.:

AF XY:

0.0000581

AC XY:

AN XY:

671328

show subpopulations

Gnomad4 AFR exome

AF:

0.0000650

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.0000226

Gnomad4 NFE exome

AF:

0.0000703

Gnomad4 OTH exome

AF:

0.000106

GnomAD4 genome

AF:

0.0000197

AC:

AN:

152256

Hom.:

Cov.:

AF XY:

0.0000134

AC XY:

AN XY:

74386

show subpopulations

Gnomad4 AFR

AF:

0.0000241

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000294

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000453

ExAC

AF:

0.0000118

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Apr 15, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.23C>A (p.A8E) alteration is located in exon 1 (coding exon 1) of the NOL7 gene. This alteration results from a C to A substitution at nucleotide position 23, causing the alanine (A) at amino acid position 8 to be replaced by a glutamic acid (E). 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

0.20

BayesDel_addAF

Benign

-0.29

BayesDel_noAF

Benign

-0.47

CADD

Benign

DANN

Benign

0.97

DEOGEN2

Benign

0.017

Eigen

Benign

-0.99

Eigen_PC

Benign

-0.98

FATHMM_MKL

Benign

0.14

LIST_S2

Benign

0.65

M_CAP

Benign

0.032

MetaRNN

Benign

0.030

MetaSVM

Benign

-0.94

MutationAssessor

Benign

0.90

PrimateAI

Uncertain

0.75

PROVEAN

Benign

-0.25

REVEL

Benign

0.099

Sift

Benign

0.33

Sift4G

Benign

0.77

Polyphen

0.020

Vest4

0.23

MVP

0.076

MPC

1.1

ClinPred

0.19

GERP RS

-0.40

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.062

gMVP

0.12

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