11-72004284-C-G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_006185.4(NUMA1):ā€‹c.6064G>Cā€‹(p.Gly2022Arg) 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 152,204 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: š‘“ 0.0000066 ( 0 hom., cov: 32)

Consequence

NUMA1
NM_006185.4 missense

Scores

1
9
9

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.10
Variant links:
Genes affected
NUMA1 (HGNC:8059): (nuclear mitotic apparatus protein 1) This gene encodes a large protein that forms a structural component of the nuclear matrix. The encoded protein interacts with microtubules and plays a role in the formation and organization of the mitotic spindle during cell division. Chromosomal translocation of this gene with the RARA (retinoic acid receptor, alpha) gene on chromosome 17 have been detected in patients with acute promyelocytic leukemia. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Nov 2013]
IL18BP (HGNC:5987): (interleukin 18 binding protein) The protein encoded by this gene functions as an inhibitor of the proinflammatory cytokine, IL18. It binds IL18, prevents the binding of IL18 to its receptor, and thus inhibits IL18-induced IFN-gamma production, resulting in reduced T-helper type 1 immune responses. This protein is constitutively expressed and secreted in mononuclear cells. Elevated level of this protein is detected in the intestinal tissues of patients with Crohn's disease. Alternatively spliced transcript variants encoding different isoforms have been described for this gene. [provided by RefSeq, Feb 2011]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.21086714).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
NUMA1NM_006185.4 linkc.6064G>C p.Gly2022Arg missense_variant Exon 25 of 27 ENST00000393695.8 NP_006176.2 Q14980-1Q3SYK8Q4LE64

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
NUMA1ENST00000393695.8 linkc.6064G>C p.Gly2022Arg missense_variant Exon 25 of 27 1 NM_006185.4 ENSP00000377298.4 Q14980-1

Frequencies

GnomAD3 genomes
AF:
0.00000657
AC:
1
AN:
152204
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0000241
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:
0.00000399
AC:
1
AN:
250574
Hom.:
0
AF XY:
0.00
AC XY:
0
AN XY:
135520
show subpopulations
Gnomad AFR exome
AF:
0.0000616
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:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
Cov.:
33
GnomAD4 genome
AF:
0.00000657
AC:
1
AN:
152204
Hom.:
0
Cov.:
32
AF XY:
0.00
AC XY:
0
AN XY:
74350
show subpopulations
Gnomad4 AFR
AF:
0.0000241
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

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
0.39
BayesDel_addAF
Benign
-0.20
T
BayesDel_noAF
Benign
-0.34
CADD
Uncertain
24
DANN
Pathogenic
1.0
DEOGEN2
Benign
0.16
.;.;T;.;.;.
Eigen
Benign
0.19
Eigen_PC
Uncertain
0.30
FATHMM_MKL
Uncertain
0.91
D
LIST_S2
Uncertain
0.92
.;.;D;D;D;D
M_CAP
Benign
0.027
D
MetaRNN
Benign
0.21
T;T;T;T;T;T
MetaSVM
Benign
-0.91
T
MutationAssessor
Uncertain
2.3
.;.;M;.;.;.
PrimateAI
Uncertain
0.54
T
PROVEAN
Uncertain
-3.0
D;D;D;.;.;.
REVEL
Benign
0.20
Sift
Uncertain
0.0070
D;D;D;.;.;.
Sift4G
Uncertain
0.059
T;D;D;D;T;D
Polyphen
1.0, 1.0
.;D;D;D;.;.
Vest4
0.26
MutPred
0.27
.;.;Loss of loop (P = 0.0128);.;.;.;
MVP
0.35
MPC
1.1
ClinPred
0.95
D
GERP RS
5.3
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
Varity_R
0.29
gMVP
0.25

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: rs1293833861; hg19: chr11-71715330; API