Genetic Variant NUMA1:p.Gln779Gln (chr11-72015166-C-T) – ACMG Classification: Benign (-13 pts)

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_StrongBP7BA1

The NM_006185.4(NUMA1):c.2337G>A(p.Gln779Gln) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0123 in 1,613,496 control chromosomes in the GnomAD database, including 319 homozygotes. 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: 𝑓 0.025 ( 91 hom., cov: 33)

Exomes 𝑓: 0.011 ( 228 hom. )

Consequence

NUMA1
NM_006185.4 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.671

Publications

12 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:

ENSG00000251143 (HGNC:58252):

ENSG00000251143 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.81).

BP7

Synonymous conserved (PhyloP=0.671 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0604 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NUMA1	NM_006185.4 link	c.2337G>A	p.Gln779Gln	synonymous_variant	Exon 15 of 27	ENST00000393695.8	NP_006176.2	Q14980-1Q3SYK8Q4LE64

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NUMA1	ENST00000393695.8 link	c.2337G>A	p.Gln779Gln	synonymous_variant	Exon 15 of 27	1	NM_006185.4	ENSP00000377298.4		Q14980-1

Frequencies

GnomAD3 genomes

AF:

0.0251

AC:

3829

AN:

152264

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0620

Gnomad AMI

AF:

0.0263

Gnomad AMR

AF:

0.0120

Gnomad ASJ

AF:

0.00980

Gnomad EAS

AF:

0.0660

Gnomad SAS

AF:

0.0209

Gnomad FIN

AF:

0.000659

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00748

Gnomad OTH

AF:

0.0263

GnomAD2 exomes

AF:

0.0154

AC:

3834

AN:

249144

AF XY:

0.0145

show subpopulations

Gnomad AFR exome

AF:

0.0657

Gnomad AMR exome

AF:

0.00495

Gnomad ASJ exome

AF:

0.0117

Gnomad EAS exome

AF:

0.0585

Gnomad FIN exome

AF:

0.00103

Gnomad NFE exome

AF:

0.00742

Gnomad OTH exome

AF:

0.0118

GnomAD4 exome

AF:

0.0110

AC:

16047

AN:

1461114

Hom.:

228

Cov.:

AF XY:

0.0109

AC XY:

7941

AN XY:

726884

show subpopulations

African (AFR)

AF:

0.0658

AC:

2202

AN:

33480

American (AMR)

AF:

0.00648

AC:

290

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.0119

AC:

311

AN:

26136

East Asian (EAS)

AF:

0.0580

AC:

2304

AN:

39700

South Asian (SAS)

AF:

0.0164

AC:

1416

AN:

86258

European-Finnish (FIN)

AF:

0.00135

AC:

AN:

52658

Middle Eastern (MID)

AF:

0.0107

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.00757

AC:

8421

AN:

1112008

Other (OTH)

AF:

0.0161

AC:

970

AN:

60382

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.486

Heterozygous variant carriers

1171

2342

3512

4683

5854

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

386

772

1158

1544

1930

<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

AF:

0.0251

AC:

3832

AN:

152382

Hom.:

Cov.:

AF XY:

0.0249

AC XY:

1852

AN XY:

74522

show subpopulations

African (AFR)

AF:

0.0618

AC:

2569

AN:

41586

American (AMR)

AF:

0.0120

AC:

184

AN:

15308

Ashkenazi Jewish (ASJ)

AF:

0.00980

AC:

AN:

3470

East Asian (EAS)

AF:

0.0661

AC:

343

AN:

5186

South Asian (SAS)

AF:

0.0207

AC:

100

AN:

4832

European-Finnish (FIN)

AF:

0.000659

AC:

AN:

10630

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00748

AC:

509

AN:

68048

Other (OTH)

AF:

0.0293

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.493

Heterozygous variant carriers

199

398

596

795

994

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

126

168

210

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0155

Hom.:

Bravo

AF:

0.0286

Asia WGS

AF:

0.0510

AC:

176

AN:

3478

EpiCase

AF:

0.00774

EpiControl

AF:

0.00907

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.81

CADD

Benign

(source)

DANN

Benign

0.61

PhyloP100

0.67

Mutation Taster

=100/0

polymorphism (auto)

(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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over