Genetic Variant NUMA1:p.Ala794Asp (chr11-72015122-G-T) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_006185.4(NUMA1):c.2381C>A(p.Ala794Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,140 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict 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)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

NUMA1
NM_006185.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 3.45

Publications

0 publications found

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]

NUMA1 links:

NUMA1-AS1 (HGNC:58252):

NUMA1-AS1 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.21226504).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006185.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
NUMA1	NM_006185.4	MANE Select	c.2381C>A	p.Ala794Asp	missense	Exon 15 of 27	NP_006176.2	Q14980-1
NUMA1	NM_001286561.2		c.2381C>A	p.Ala794Asp	missense	Exon 16 of 27	NP_001273490.1	Q14980-2
NUMA1-AS1	NR_104178.2		n.832G>T		non_coding_transcript_exon	Exon 1 of 4

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
NUMA1	ENST00000393695.8	TSL:1 MANE Select	c.2381C>A	p.Ala794Asp	missense	Exon 15 of 27	ENSP00000377298.4	Q14980-1
NUMA1	ENST00000351960.10	TSL:1	c.1242+1286C>A		intron	N/A	ENSP00000260051.8	Q14980-5
NUMA1	ENST00000967521.1		c.2381C>A	p.Ala794Asp	missense	Exon 15 of 28	ENSP00000637580.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461140

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

726896

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33480

American (AMR)

AF:

0.00

AC:

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26136

East Asian (EAS)

AF:

0.00

AC:

AN:

39700

South Asian (SAS)

AF:

0.00

AC:

AN:

86258

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52680

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

8.99e-7

AC:

AN:

1112006

Other (OTH)

AF:

0.00

AC:

AN:

60388

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.16

BayesDel_addAF

Benign

-0.036

BayesDel_noAF

Benign

-0.29

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.057

Eigen

Uncertain

0.31

Eigen_PC

Uncertain

0.25

FATHMM_MKL

Uncertain

0.77

LIST_S2

Benign

0.83

M_CAP

Benign

0.014

MetaRNN

Benign

0.21

MetaSVM

Benign

-0.63

MutationAssessor

Uncertain

2.4

PhyloP100

3.5

PrimateAI

Benign

0.39

PROVEAN

Benign

-0.87

REVEL

Benign

0.18

Sift

Uncertain

0.0030

Sift4G

Uncertain

0.045

Polyphen

0.97

Vest4

0.38

MutPred

0.056

Gain of phosphorylation at T798 (P = 0.29)

MVP

0.30

MPC

1.1

ClinPred

0.74

GERP RS

5.9

RBP_binding_hub_radar

1.1

RBP_regulation_power_radar

2.8

Varity_R

0.30

gMVP

0.20

Mutation Taster

=81/19

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over