9-92306981-T-A

Position:

chr9-92306981-T-A

Variant summary

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

The NM_017948.6(NOL8):c.2730A>T(p.Glu910Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000725 in 1,612,952 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.000072 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000073 ( 0 hom. )

Consequence

NOL8
NM_017948.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.0650

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:

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=0.03132227).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NOL8	NM_017948.6 linkuse as main transcript	c.2730A>T	p.Glu910Asp	missense_variant	11/17	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.2730A>T	p.Glu910Asp	missense_variant	11/17	1	NM_017948.6	ENSP00000401177.2	Q76FK4-1
NOL8	ENST00000542053.5 linkuse as main transcript	c.2526A>T	p.Glu842Asp	missense_variant	10/16	5		ENSP00000440709.1	Q76FK4-2
NOL8	ENST00000432670.6 linkuse as main transcript	c.2730A>T	p.Glu910Asp	missense_variant	11/13	5		ENSP00000414112.2	F8WE42
NOL8	ENST00000360868.7 linkuse as main transcript	n.*2585A>T		non_coding_transcript_exon_variant	11/17	2		ENSP00000354115.3	F5GXV1
NOL8	ENST00000434228.5 linkuse as main transcript	n.*3022A>T		non_coding_transcript_exon_variant	13/13	2		ENSP00000415750.1	F5GXV1
NOL8	ENST00000360868.7 linkuse as main transcript	n.*2585A>T		3_prime_UTR_variant	11/17	2		ENSP00000354115.3	F5GXV1
NOL8	ENST00000434228.5 linkuse as main transcript	n.*3022A>T		3_prime_UTR_variant	13/13	2		ENSP00000415750.1	F5GXV1

Frequencies

GnomAD3 genomes

AF:

0.0000722

AC:

AN:

152252

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00115

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000882

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000683

AC:

AN:

248746

Hom.:

AF XY:

0.0000889

AC XY:

AN XY:

134936

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000291

Gnomad ASJ exome

AF:

0.000497

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000976

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000726

AC:

106

AN:

1460700

Hom.:

Cov.:

AF XY:

0.0000702

AC XY:

AN XY:

726608

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000224

Gnomad4 ASJ exome

AF:

0.00115

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000630

Gnomad4 OTH exome

AF:

0.0000829

GnomAD4 genome

AF:

0.0000722

AC:

AN:

152252

Hom.:

Cov.:

AF XY:

0.000108

AC XY:

AN XY:

74380

show subpopulations

Gnomad4 AFR

AF:

0.0000241

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00115

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000882

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000201

Hom.:

Bravo

AF:

0.0000756

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000123

AC:

ExAC

AF:

0.0000745

AC:

EpiCase

AF:

0.000218

EpiControl

AF:

0.0000593

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

Sep 20, 2024

The c.2730A>T (p.E910D) alteration is located in exon 11 (coding exon 10) of the NOL8 gene. This alteration results from a A to T substitution at nucleotide position 2730, causing the glutamic acid (E) at amino acid position 910 to be replaced by an aspartic acid (D). 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

0.14

BayesDel_addAF

Benign

-0.40

BayesDel_noAF

Benign

-0.62

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.0054

T;.;T;.;.;T

Eigen

Benign

-0.45

Eigen_PC

Benign

-0.30

FATHMM_MKL

Benign

0.68

LIST_S2

Benign

0.77

.;T;T;T;.;T

M_CAP

Benign

0.0099

MetaRNN

Benign

0.031

T;T;T;T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.26

N;.;N;.;.;.

PrimateAI

Benign

0.33

PROVEAN

Benign

-0.97

N;N;N;N;N;N

REVEL

Benign

0.028

Sift

Benign

0.24

T;T;T;T;T;T

Sift4G

Benign

0.26

T;T;T;T;T;.

Polyphen

0.26

B;B;B;.;B;.

Vest4

0.11

MutPred

0.24

Loss of methylation at K913 (P = 0.0973);.;Loss of methylation at K913 (P = 0.0973);.;.;Loss of methylation at K913 (P = 0.0973);

MVP

0.18

MPC

0.051

ClinPred

0.11

GERP RS

1.9

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

2.8

Varity_R

0.065

gMVP

0.067

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