chr18-34019364-A-G

Variant summary

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

The NM_003787.5(NOL4):ā€‹c.1010T>Cā€‹(p.Ile337Thr) variant causes a missense change. The variant allele was found at a frequency of 0.00000958 in 1,461,776 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā˜…).

Frequency

Genomes: not found (cov: 32)
Exomes š‘“: 0.0000096 ( 0 hom. )

Consequence

NOL4
NM_003787.5 missense

Scores

5
14

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.78
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=0.15867525).
BS2
High AC in GnomAdExome4 at 14 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
NOL4NM_003787.5 linkuse as main transcriptc.1010T>C p.Ile337Thr missense_variant 6/11 ENST00000261592.10

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
NOL4ENST00000261592.10 linkuse as main transcriptc.1010T>C p.Ile337Thr missense_variant 6/111 NM_003787.5 P1O94818-1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD3 exomes
AF:
0.0000239
AC:
6
AN:
250806
Hom.:
0
AF XY:
0.0000148
AC XY:
2
AN XY:
135562
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:
0.000196
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000958
AC:
14
AN:
1461776
Hom.:
0
Cov.:
32
AF XY:
0.0000124
AC XY:
9
AN XY:
727192
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:
0.000162
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32
ExAC
AF:
0.0000330
AC:
4
Asia WGS
AF:
0.000577
AC:
2
AN:
3478

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 GeneticsNov 15, 2021The c.1010T>C (p.I337T) alteration is located in exon 6 (coding exon 6) of the NOL4 gene. This alteration results from a T to C substitution at nucleotide position 1010, causing the isoleucine (I) at amino acid position 337 to be replaced by a threonine (T). 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
0.13
BayesDel_addAF
Benign
-0.12
T
BayesDel_noAF
Benign
-0.13
CADD
Benign
19
DANN
Uncertain
0.98
DEOGEN2
Benign
0.028
T;.;.;.;T;.
Eigen
Benign
-0.048
Eigen_PC
Benign
0.12
FATHMM_MKL
Uncertain
0.95
D
LIST_S2
Uncertain
0.95
D;D;D;D;D;D
M_CAP
Benign
0.031
D
MetaRNN
Benign
0.16
T;T;T;T;T;T
MetaSVM
Benign
-0.56
T
MutationAssessor
Benign
1.2
L;.;L;.;.;.
MutationTaster
Benign
0.95
D;D;D;D;D;D
PrimateAI
Uncertain
0.61
T
PROVEAN
Benign
-0.060
N;N;.;N;.;.
REVEL
Uncertain
0.35
Sift
Benign
0.057
T;T;.;T;.;.
Sift4G
Benign
0.39
T;T;T;T;T;T
Polyphen
0.28
B;.;B;.;.;.
Vest4
0.68
MutPred
0.30
Loss of stability (P = 0.0171);.;Loss of stability (P = 0.0171);.;.;.;
MVP
0.28
MPC
0.12
ClinPred
0.17
T
GERP RS
4.6
Varity_R
0.090
gMVP
0.37

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: rs773755694; hg19: chr18-31599328; API