chr18-34129984-G-A

Variant summary

Our verdict is Likely benign. Variant got -3 ACMG points: 1P and 4B. PP3BS2

The NM_003787.5(NOL4):​c.301C>T​(p.Arg101Trp) variant causes a missense change. The variant allele was found at a frequency of 0.00000417 in 1,440,064 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R101Q) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 31)
Exomes 𝑓: 0.0000042 ( 0 hom. )

Consequence

NOL4
NM_003787.5 missense

Scores

10
6
3

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.03
Variant links:
Genes affected
NOL4 (HGNC:7870): (nucleolar protein 4) Predicted to enable RNA binding activity. Predicted to be located in nucleolus. [provided by Alliance of Genome Resources, Apr 2022]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -3 ACMG points.

PP3
MetaRNN computational evidence supports a deleterious effect, 0.827
BS2
High AC in GnomAdExome4 at 6 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
NOL4NM_003787.5 linkuse as main transcriptc.301C>T p.Arg101Trp missense_variant 2/11 ENST00000261592.10

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
NOL4ENST00000261592.10 linkuse as main transcriptc.301C>T p.Arg101Trp missense_variant 2/111 NM_003787.5 P1O94818-1

Frequencies

GnomAD3 genomes
Cov.:
31
GnomAD3 exomes
AF:
0.00000843
AC:
2
AN:
237344
Hom.:
0
AF XY:
0.00000777
AC XY:
1
AN XY:
128740
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000183
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000417
AC:
6
AN:
1440064
Hom.:
0
Cov.:
31
AF XY:
0.00000140
AC XY:
1
AN XY:
716310
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:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000454
Gnomad4 OTH exome
AF:
0.0000169
GnomAD4 genome
Cov.:
31
ExAC
AF:
0.00000824
AC:
1

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingCeGaT Center for Human Genetics TuebingenOct 01, 2022NOL4: PP3 -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
0.82
BayesDel_addAF
Pathogenic
0.38
D
BayesDel_noAF
Pathogenic
0.30
CADD
Pathogenic
26
DANN
Pathogenic
1.0
DEOGEN2
Benign
0.32
T;.;.;T
Eigen
Uncertain
0.50
Eigen_PC
Uncertain
0.46
FATHMM_MKL
Uncertain
0.92
D
LIST_S2
Pathogenic
0.99
D;D;D;D
M_CAP
Uncertain
0.21
D
MetaRNN
Pathogenic
0.83
D;D;D;D
MetaSVM
Uncertain
0.38
D
MutationAssessor
Benign
2.0
M;M;.;.
MutationTaster
Benign
0.99
D;D;D;D;D
PrimateAI
Pathogenic
0.83
D
PROVEAN
Uncertain
-3.4
D;.;D;.
REVEL
Pathogenic
0.77
Sift
Pathogenic
0.0
D;.;D;.
Sift4G
Pathogenic
0.0010
D;D;D;D
Polyphen
1.0
D;D;.;.
Vest4
0.87
MutPred
0.60
Gain of catalytic residue at L99 (P = 0.0042);Gain of catalytic residue at L99 (P = 0.0042);.;.;
MVP
0.97
MPC
2.2
ClinPred
0.96
D
GERP RS
3.7
Varity_R
0.37
gMVP
0.93

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.

Other links and lift over

dbSNP: rs755854498; hg19: chr18-31709948; COSMIC: COSV52347295; API