Variant rs3750913 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_006185.4(NUMA1):c.2381C>G(p.Ala794Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0303 in 1,613,474 control chromosomes in the GnomAD database, including 817 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.029 ( 59 hom., cov: 33)

Exomes 𝑓: 0.031 ( 758 hom. )

Consequence

NUMA1
NM_006185.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 3.45

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:):

ENSG00000251143 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0024774969).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0674 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NUMA1	NM_006185.4 linkuse as main transcript	c.2381C>G	p.Ala794Gly	missense_variant	15/27	ENST00000393695.8	NP_006176.2	Q14980-1Q3SYK8Q4LE64

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NUMA1	ENST00000393695.8 linkuse as main transcript	c.2381C>G	p.Ala794Gly	missense_variant	15/27	1	NM_006185.4	ENSP00000377298.4		Q14980-1

Frequencies

GnomAD3 genomes

AF:

0.0287

AC:

4363

AN:

152220

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0180

Gnomad AMI

AF:

0.0570

Gnomad AMR

AF:

0.0255

Gnomad ASJ

AF:

0.0455

Gnomad EAS

AF:

0.0741

Gnomad SAS

AF:

0.0420

Gnomad FIN

AF:

0.0244

Gnomad MID

AF:

0.0601

Gnomad NFE

AF:

0.0305

Gnomad OTH

AF:

0.0345

GnomAD3 exomes

AF:

0.0340

AC:

8501

AN:

249898

Hom.:

172

AF XY:

0.0354

AC XY:

4785

AN XY:

135214

show subpopulations

Gnomad AFR exome

AF:

0.0169

Gnomad AMR exome

AF:

0.0205

Gnomad ASJ exome

AF:

0.0465

Gnomad EAS exome

AF:

0.0761

Gnomad SAS exome

AF:

0.0426

Gnomad FIN exome

AF:

0.0287

Gnomad NFE exome

AF:

0.0313

Gnomad OTH exome

AF:

0.0345

GnomAD4 exome

AF:

0.0305

AC:

44593

AN:

1461136

Hom.:

758

Cov.:

AF XY:

0.0313

AC XY:

22741

AN XY:

726896

show subpopulations

Gnomad4 AFR exome

AF:

0.0177

Gnomad4 AMR exome

AF:

0.0225

Gnomad4 ASJ exome

AF:

0.0465

Gnomad4 EAS exome

AF:

0.0631

Gnomad4 SAS exome

AF:

0.0449

Gnomad4 FIN exome

AF:

0.0289

Gnomad4 NFE exome

AF:

0.0284

Gnomad4 OTH exome

AF:

0.0335

GnomAD4 genome

AF:

0.0287

AC:

4366

AN:

152338

Hom.:

Cov.:

AF XY:

0.0296

AC XY:

2207

AN XY:

74482

show subpopulations

Gnomad4 AFR

AF:

0.0181

Gnomad4 AMR

AF:

0.0255

Gnomad4 ASJ

AF:

0.0455

Gnomad4 EAS

AF:

0.0735

Gnomad4 SAS

AF:

0.0424

Gnomad4 FIN

AF:

0.0244

Gnomad4 NFE

AF:

0.0305

Gnomad4 OTH

AF:

0.0336

Alfa

AF:

0.0323

Hom.:

Bravo

AF:

0.0289

TwinsUK

AF:

0.0237

AC:

ALSPAC

AF:

0.0244

AC:

ESP6500AA

AF:

0.0189

AC:

ESP6500EA

AF:

0.0274

AC:

235

ExAC

AF:

0.0341

AC:

4146

Asia WGS

AF:

0.0480

AC:

170

AN:

3478

EpiCase

AF:

0.0335

EpiControl

AF:

0.0332

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.12

BayesDel_addAF

Benign

-0.51

BayesDel_noAF

Benign

-0.45

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.079

.;T;.;.;T

Eigen

Benign

-0.19

Eigen_PC

Benign

-0.11

FATHMM_MKL

Benign

0.50

LIST_S2

Benign

0.64

.;T;T;T;T

MetaRNN

Benign

0.0025

T;T;T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.4

M;M;M;.;.

PrimateAI

Benign

0.36

PROVEAN

Benign

-1.3

N;N;.;.;N

REVEL

Benign

0.072

Sift

Uncertain

0.015

D;D;.;.;T

Sift4G

Uncertain

0.052

T;D;T;D;.

Polyphen

0.031

B;B;B;.;.

Vest4

0.12

MPC

0.73

ClinPred

0.031

GERP RS

5.9

Varity_R

0.15

gMVP

0.031

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over