Variant chr6-13615575-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_016167.5(NOL7):c.217C>A(p.Gln73Lys) 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. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

NOL7
NM_016167.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.27

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:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.07335845).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NOL7	NM_016167.5 link	c.217C>A	p.Gln73Lys	missense_variant	1/8	ENST00000451315.7	NP_057251.2	Q9UMY1-1A0A024QZW2
NOL7	NM_001317724.2 link	c.217C>A	p.Gln73Lys	missense_variant	1/9		NP_001304653.1	Q9UMY1-1A0A024QZW2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
NOL7	ENST00000451315.7 link	c.217C>A	p.Gln73Lys	missense_variant	1/8	1	NM_016167.5	ENSP00000405674.2	Q9UMY1-1
NOL7	ENST00000420088.1 link	c.28C>A	p.Gln10Lys	missense_variant	1/4	2		ENSP00000404836.1	H7C2B1
NOL7	ENST00000474485.1 link	n.-14C>A		upstream_gene_variant		3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.00000141

AC:

AN:

1420260

Hom.:

Cov.:

AF XY:

0.00000285

AC XY:

AN XY:

702978

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000266

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

9.18e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Oct 04, 2024

The c.217C>A (p.Q73K) 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 217, causing the glutamine (Q) at amino acid position 73 to be replaced by a lysine (K). 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

0.15

BayesDel_addAF

Benign

-0.21

BayesDel_noAF

Benign

-0.54

CADD

Benign

DANN

Benign

0.97

DEOGEN2

Benign

0.0058

Eigen

Benign

-0.29

Eigen_PC

Benign

-0.084

FATHMM_MKL

Benign

0.36

LIST_S2

Benign

0.71

M_CAP

Benign

0.016

MetaRNN

Benign

0.073

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.1

PrimateAI

Uncertain

0.74

PROVEAN

Benign

0.35

REVEL

Benign

0.035

Sift

Benign

0.53

Sift4G

Benign

0.69

Polyphen

0.022

Vest4

0.16

MutPred

0.23

Gain of ubiquitination at Q73 (P = 0.0066);

MVP

0.32

MPC

0.50

ClinPred

0.47

GERP RS

3.8

Varity_R

0.32

gMVP

0.060

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

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over