11-72003981-C-G

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_006185.4(NUMA1):​c.6242G>C​(p.Arg2081Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 33)

Consequence

NUMA1
NM_006185.4 missense

Scores

10
9

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.51
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]

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.27573004).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
NUMA1NM_006185.4 linkc.6242G>C p.Arg2081Pro missense_variant Exon 26 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.6242G>C p.Arg2081Pro missense_variant Exon 26 of 27 1 NM_006185.4 ENSP00000377298.4 Q14980-1

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
Cov.:
33
GnomAD4 genome
Cov.:
33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.26
BayesDel_addAF
Uncertain
0.056
T
BayesDel_noAF
Benign
-0.16
CADD
Benign
22
DANN
Uncertain
1.0
DEOGEN2
Benign
0.17
.;.;T;.;.;.
Eigen
Uncertain
0.40
Eigen_PC
Uncertain
0.42
FATHMM_MKL
Uncertain
0.93
D
LIST_S2
Uncertain
0.88
.;.;D;D;D;D
M_CAP
Benign
0.033
D
MetaRNN
Benign
0.28
T;T;T;T;T;T
MetaSVM
Benign
-1.0
T
MutationAssessor
Uncertain
2.3
.;.;M;.;.;.
PrimateAI
Benign
0.44
T
PROVEAN
Uncertain
-2.7
D;N;N;.;.;.
REVEL
Benign
0.18
Sift
Uncertain
0.0030
D;D;D;.;.;.
Sift4G
Uncertain
0.017
D;D;D;D;D;D
Polyphen
0.99, 0.95
.;D;P;D;.;.
Vest4
0.37
MutPred
0.42
.;.;Gain of relative solvent accessibility (P = 0.0098);.;.;.;
MVP
0.37
MPC
0.90
ClinPred
0.95
D
GERP RS
4.9
Varity_R
0.37
gMVP
0.26

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr11-71715027; API