chr9-92298949-G-A

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate

The NM_017948.6(NOL8):​c.3308C>T​(p.Ala1103Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000657 in 152,166 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0 ( 0 hom. )
Failed GnomAD Quality Control

Consequence

NOL8
NM_017948.6 missense

Scores

19

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.965
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.015555143).
BP6
Variant 9-92298949-G-A is Benign according to our data. Variant chr9-92298949-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 2315719.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
NOL8NM_017948.6 linkuse as main transcriptc.3308C>T p.Ala1103Val missense_variant 15/17 ENST00000442668.7 NP_060418.4

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
NOL8ENST00000442668.7 linkuse as main transcriptc.3308C>T p.Ala1103Val missense_variant 15/171 NM_017948.6 ENSP00000401177 P2Q76FK4-1

Frequencies

GnomAD3 genomes
AF:
0.00000657
AC:
1
AN:
152166
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.0000654
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
GnomAD4 exome
Data not reliable, filtered out with message: AC0;AS_VQSR
AF:
0.00
AC:
0
AN:
1363738
Hom.:
0
Cov.:
26
AF XY:
0.00
AC XY:
0
AN XY:
671990
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:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.00000657
AC:
1
AN:
152166
Hom.:
0
Cov.:
32
AF XY:
0.00
AC XY:
0
AN XY:
74334
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.0000654
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

ClinVar

Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Benign:1
Likely benign, criteria provided, single submitterclinical testingAmbry GeneticsOct 03, 2022This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.077
BayesDel_addAF
Benign
-0.47
T
BayesDel_noAF
Benign
-0.92
CADD
Benign
1.1
DANN
Benign
0.23
DEOGEN2
Benign
0.0024
T;.;T;.;.
Eigen
Benign
-1.8
Eigen_PC
Benign
-1.8
FATHMM_MKL
Benign
0.0045
N
LIST_S2
Benign
0.71
.;T;T;T;.
M_CAP
Benign
0.0025
T
MetaRNN
Benign
0.016
T;T;T;T;T
MetaSVM
Benign
-0.97
T
MutationAssessor
Benign
-0.30
N;.;N;.;.
MutationTaster
Benign
1.0
N;N;N;N;N
PrimateAI
Benign
0.24
T
PROVEAN
Benign
-0.50
N;N;N;N;N
REVEL
Benign
0.0050
Sift
Benign
0.73
T;T;T;T;T
Sift4G
Benign
0.58
T;T;T;T;T
Polyphen
0.0
B;B;B;.;B
Vest4
0.014
MutPred
0.16
Gain of sheet (P = 0.0149);.;Gain of sheet (P = 0.0149);.;.;
MVP
0.20
MPC
0.052
ClinPred
0.028
T
GERP RS
-7.4
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.1
Varity_R
0.028
gMVP
0.036

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.050
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.

Other links and lift over

dbSNP: rs1229271123; hg19: chr9-95061231; API