18-34019427-G-A

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_003787.5(NOL4):​c.947C>T​(p.Thr316Ile) variant causes a missense change. The variant allele was found at a frequency of 0.0000198 in 1,613,890 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000033 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000018 ( 0 hom. )

Consequence

NOL4
NM_003787.5 missense

Scores

1
10
8

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.03
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 -6 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.19476658).
BS2
High AC in GnomAd4 at 5 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
NOL4NM_003787.5 linkuse as main transcriptc.947C>T p.Thr316Ile missense_variant 6/11 ENST00000261592.10

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
NOL4ENST00000261592.10 linkuse as main transcriptc.947C>T p.Thr316Ile missense_variant 6/111 NM_003787.5 P1O94818-1

Frequencies

GnomAD3 genomes
AF:
0.0000329
AC:
5
AN:
151954
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000328
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:
0.0000877
AC:
22
AN:
250802
Hom.:
0
AF XY:
0.000103
AC XY:
14
AN XY:
135514
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.000636
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:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000185
AC:
27
AN:
1461818
Hom.:
0
Cov.:
32
AF XY:
0.0000220
AC XY:
16
AN XY:
727216
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.000604
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:
0.0000329
AC:
5
AN:
152072
Hom.:
0
Cov.:
32
AF XY:
0.0000135
AC XY:
1
AN XY:
74334
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.000328
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
Alfa
AF:
0.0000868
Hom.:
0
Bravo
AF:
0.0000642
ExAC
AF:
0.0000659
AC:
8

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 submitterclinical testingAmbry GeneticsJul 08, 2022The c.947C>T (p.T316I) alteration is located in exon 6 (coding exon 6) of the NOL4 gene. This alteration results from a C to T substitution at nucleotide position 947, causing the threonine (T) at amino acid position 316 to be replaced by an isoleucine (I). 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
-0.070
T
BayesDel_noAF
Uncertain
0.040
CADD
Uncertain
24
DANN
Pathogenic
1.0
DEOGEN2
Benign
0.052
T;.;.;.;T;.
Eigen
Uncertain
0.41
Eigen_PC
Uncertain
0.51
FATHMM_MKL
Uncertain
0.91
D
LIST_S2
Uncertain
0.94
D;D;D;D;D;D
M_CAP
Benign
0.044
D
MetaRNN
Benign
0.19
T;T;T;T;T;T
MetaSVM
Uncertain
0.37
D
MutationAssessor
Uncertain
2.6
M;.;M;.;.;.
MutationTaster
Benign
0.96
D;D;D;D;D;D
PrimateAI
Uncertain
0.72
T
PROVEAN
Benign
-1.3
N;N;.;N;.;.
REVEL
Uncertain
0.50
Sift
Uncertain
0.014
D;D;.;D;.;.
Sift4G
Benign
0.30
T;T;T;T;T;T
Polyphen
0.87
P;.;P;.;.;.
Vest4
0.68
MutPred
0.23
Gain of sheet (P = 0.1208);.;Gain of sheet (P = 0.1208);.;.;.;
MVP
0.43
MPC
0.23
ClinPred
0.18
T
GERP RS
5.8
Varity_R
0.13
gMVP
0.51

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: rs772761092; hg19: chr18-31599391; API