Variant 9-92299972-G-T 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_017948.6(NOL8):c.3220C>A(p.Gln1074Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000363 in 1,461,306 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.000036 ( 0 hom. )

Consequence

NOL8
NM_017948.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.01

Variant links:

Genes affected

NOL8 (HGNC:23387): (nucleolar protein 8) NOL8 binds Ras-related GTP-binding proteins (see MIM 608267) and plays a role in cell growth (Sekiguchi et al., 2004 [PubMed 14660641]).[supplied by OMIM, Mar 2008]

NOL8 links:

NOL8 (HGNC:):

NOL8 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=0.09216109).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NOL8	NM_017948.6 linkuse as main transcript	c.3220C>A	p.Gln1074Lys	missense_variant	14/17	ENST00000442668.7	NP_060418.4	Q76FK4-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
NOL8	ENST00000442668.7 linkuse as main transcript	c.3220C>A	p.Gln1074Lys	missense_variant	14/17	1	NM_017948.6	ENSP00000401177.2	Q76FK4-1
NOL8	ENST00000542053.5 linkuse as main transcript	c.3016C>A	p.Gln1006Lys	missense_variant	13/16	5		ENSP00000440709.1	Q76FK4-2
NOL8	ENST00000360868.7 linkuse as main transcript	n.*3075C>A		non_coding_transcript_exon_variant	14/17	2		ENSP00000354115.3	F5GXV1
NOL8	ENST00000360868.7 linkuse as main transcript	n.*3075C>A		3_prime_UTR_variant	14/17	2		ENSP00000354115.3	F5GXV1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.0000363

AC:

AN:

1461306

Hom.:

Cov.:

AF XY:

0.0000358

AC XY:

AN XY:

726956

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000116

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000450

Gnomad4 OTH exome

AF:

0.0000331

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 21, 2024

The c.3220C>A (p.Q1074K) alteration is located in exon 14 (coding exon 13) of the NOL8 gene. This alteration results from a C to A substitution at nucleotide position 3220, causing the glutamine (Q) at amino acid position 1074 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

0.065

BayesDel_addAF

Benign

-0.28

BayesDel_noAF

Benign

-0.64

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.021

T;.;T;.;.

Eigen

Benign

-0.19

Eigen_PC

Benign

-0.10

FATHMM_MKL

Uncertain

0.92

LIST_S2

Benign

0.65

.;T;T;T;.

M_CAP

Benign

0.0039

MetaRNN

Benign

0.092

T;T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Uncertain

2.1

M;.;M;.;.

PrimateAI

Benign

0.28

PROVEAN

Benign

-1.9

N;N;N;N;N

REVEL

Benign

0.082

Sift

Benign

0.099

T;T;T;T;T

Sift4G

Benign

0.090

T;T;T;T;T

Polyphen

0.058

B;B;B;.;B

Vest4

0.17

MutPred

0.27

Gain of methylation at Q1074 (P = 0.0014);.;Gain of methylation at Q1074 (P = 0.0014);.;.;

MVP

0.14

MPC

0.082

ClinPred

0.29

GERP RS

1.8

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.065

gMVP

0.17

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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