Variant rs587783252 details in Genebe, Genetics Data Aggregator

Variant summary

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

The ENST00000367409.9(ASPM):c.59C>T(p.Pro20Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000497 in 1,608,178 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 31)

Exomes 𝑓: 0.0000048 ( 0 hom. )

Consequence

ASPM
ENST00000367409.9 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.01

Variant links:

Genes affected

ASPM (HGNC:19048): (assembly factor for spindle microtubules) This gene is the human ortholog of the Drosophila melanogaster 'abnormal spindle' gene (asp), which is essential for normal mitotic spindle function in embryonic neuroblasts. Studies in mouse also suggest a role of this gene in mitotic spindle regulation, with a preferential role in regulating neurogenesis. Mutations in this gene are associated with microcephaly primary type 5. Multiple transcript variants encoding different isoforms have been found for this gene.[provided by RefSeq, May 2011]

ASPM links:

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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=0.10597557).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ASPM	NM_018136.5 linkuse as main transcript	c.59C>T	p.Pro20Leu	missense_variant	1/28	ENST00000367409.9	NP_060606.3
ASPM	NM_001206846.2 linkuse as main transcript	c.59C>T	p.Pro20Leu	missense_variant	1/27		NP_001193775.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ASPM	ENST00000367409.9 linkuse as main transcript	c.59C>T	p.Pro20Leu	missense_variant	1/28	1	NM_018136.5	ENSP00000356379	P1	Q8IZT6-1

Frequencies

GnomAD3 genomes

AF:

0.00000658

AC:

AN:

151912

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000242

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:

0.00000868

AC:

AN:

230472

Hom.:

AF XY:

0.00000781

AC XY:

AN XY:

128000

show subpopulations

Gnomad AFR exome

AF:

0.0000763

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:

0.0000496

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000481

AC:

AN:

1456266

Hom.:

Cov.:

AF XY:

0.00000276

AC XY:

AN XY:

724170

show subpopulations

Gnomad4 AFR exome

AF:

0.000120

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.0000197

Gnomad4 NFE exome

AF:

9.00e-7

Gnomad4 OTH exome

AF:

0.0000167

GnomAD4 genome

AF:

0.00000658

AC:

AN:

151912

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74144

show subpopulations

Gnomad4 AFR

AF:

0.0000242

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

Alfa

AF:

0.0000508

Hom.:

ExAC

AF:

0.00000851

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Microcephaly 5, primary, autosomal recessive

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Genetic Services Laboratory, University of Chicago

Feb 08, 2013

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.085

BayesDel_addAF

Benign

-0.12

BayesDel_noAF

Benign

-0.41

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.030

T;.

Eigen

Benign

-0.59

Eigen_PC

Benign

-0.69

FATHMM_MKL

Benign

0.11

LIST_S2

Benign

0.71

T;T

M_CAP

Benign

0.021

MetaRNN

Benign

0.11

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.7

L;L

MutationTaster

Benign

1.0

N;N

PrimateAI

Uncertain

0.65

PROVEAN

Benign

-1.9

N;N

REVEL

Benign

0.047

Sift

Uncertain

0.011

D;D

Sift4G

Benign

0.13

T;T

Polyphen

0.80

P;.

Vest4

0.13

MutPred

0.16

Loss of catalytic residue at P20 (P = 0.0265);Loss of catalytic residue at P20 (P = 0.0265);

MVP

0.54

ClinPred

0.11

GERP RS

2.4

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

2.6

Varity_R

0.051

gMVP

0.23

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over