9-92311234-G-A

Position:

chr9-92311234-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 4P and 2B. PM1PM2BP4_Moderate

The NM_017948.6(NOL8):c.2384C>T(p.Thr795Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000496 in 1,613,672 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 0.000013 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000041 ( 0 hom. )

Consequence

NOL8
NM_017948.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.922

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 Uncertain_significance. Variant got 2 ACMG points.

PM1

In a modified_residue Phosphothreonine (size 0) in uniprot entity NOL8_HUMAN

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.093132466).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NOL8	NM_017948.6 linkuse as main transcript	c.2384C>T	p.Thr795Met	missense_variant	8/17	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.2384C>T	p.Thr795Met	missense_variant	8/17	1	NM_017948.6	ENSP00000401177.2	Q76FK4-1
NOL8	ENST00000542053.5 linkuse as main transcript	c.2180C>T	p.Thr727Met	missense_variant	7/16	5		ENSP00000440709.1	Q76FK4-2
NOL8	ENST00000432670.6 linkuse as main transcript	c.2384C>T	p.Thr795Met	missense_variant	8/13	5		ENSP00000414112.2	F8WE42
NOL8	ENST00000360868.7 linkuse as main transcript	n.*2239C>T		non_coding_transcript_exon_variant	8/17	2		ENSP00000354115.3	F5GXV1
NOL8	ENST00000434228.5 linkuse as main transcript	n.*2676C>T		non_coding_transcript_exon_variant	10/13	2		ENSP00000415750.1	F5GXV1
NOL8	ENST00000360868.7 linkuse as main transcript	n.*2239C>T		3_prime_UTR_variant	8/17	2		ENSP00000354115.3	F5GXV1
NOL8	ENST00000434228.5 linkuse as main transcript	n.*2676C>T		3_prime_UTR_variant	10/13	2		ENSP00000415750.1	F5GXV1

Frequencies

GnomAD3 genomes

AF:

0.0000131

AC:

AN:

152146

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000483

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000201

AC:

AN:

248836

Hom.:

AF XY:

0.0000148

AC XY:

AN XY:

134980

show subpopulations

Gnomad AFR exome

AF:

0.000129

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000655

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000887

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000411

AC:

AN:

1461408

Hom.:

Cov.:

AF XY:

0.00000275

AC XY:

AN XY:

727002

show subpopulations

Gnomad4 AFR exome

AF:

0.0000299

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000348

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000180

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000131

AC:

AN:

152264

Hom.:

Cov.:

AF XY:

0.0000269

AC XY:

AN XY:

74456

show subpopulations

Gnomad4 AFR

AF:

0.0000481

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:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.00000378

ESP6500AA

AF:

0.000253

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.0000414

AC:

EpiCase

AF:

0.00

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

Oct 24, 2024

The c.2384C>T (p.T795M) alteration is located in exon 8 (coding exon 7) of the NOL8 gene. This alteration results from a C to T substitution at nucleotide position 2384, causing the threonine (T) at amino acid position 795 to be replaced by a methionine (M). 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

0.11

BayesDel_addAF

Benign

-0.37

BayesDel_noAF

Benign

-0.49

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.077

T;.;T;.;T

Eigen

Benign

-0.27

Eigen_PC

Benign

-0.29

FATHMM_MKL

Benign

0.45

LIST_S2

Benign

0.77

.;T;T;.;T

M_CAP

Benign

0.019

MetaRNN

Benign

0.093

T;T;T;T;T

MetaSVM

Benign

-0.92

MutationAssessor

Benign

1.8

L;.;L;.;.

PrimateAI

Benign

0.36

PROVEAN

Uncertain

-3.0

D;D;D;D;D

REVEL

Benign

0.073

Sift

Uncertain

0.0050

D;D;D;D;D

Sift4G

Uncertain

0.042

D;D;D;D;.

Polyphen

0.90

P;P;P;P;.

Vest4

0.51

MVP

0.39

MPC

0.080

ClinPred

0.36

GERP RS

3.3

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.085

gMVP

0.16

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.10

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