Genetic Variant ASPM:c.10332-6dupT (chr1-197084431-T-TA) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_ModerateBA1

The NM_018136.5(ASPM):c.10332-6dupT variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.33 ( 8679 hom., cov: 0)

Exomes 𝑓: 0.31 ( 2077 hom. )

Failed GnomAD Quality Control

Consequence

ASPM
NM_018136.5 splice_region, intron

Scores

Not classified

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.439

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 was made for transcript

Our verdict: Benign. The variant received -10 ACMG points.

BP6

Variant 1-197084431-T-TA is Benign according to our data. Variant chr1-197084431-T-TA is described in ClinVar as [Benign]. Clinvar id is 1238332.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.436 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ASPM	NM_018136.5 link	c.10332-6dupT		splice_region_variant, intron_variant	Intron 27 of 27	ENST00000367409.9	NP_060606.3	Q8IZT6-1B3KWI2
ASPM	NM_001206846.2 link	c.5577-6dupT		splice_region_variant, intron_variant	Intron 26 of 26		NP_001193775.1	Q8IZT6-2B3KWI2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ASPM	ENST00000367409.9 link	c.10332-6_10332-5insT		splice_region_variant, intron_variant	Intron 27 of 27	1	NM_018136.5	ENSP00000356379.4		Q8IZT6-1

Frequencies

GnomAD3 genomes

AF:

0.334

AC:

47758

AN:

143130

Hom.:

8683

Cov.:

show subpopulations

Gnomad AFR

AF:

0.174

Gnomad AMI

AF:

0.413

Gnomad AMR

AF:

0.287

Gnomad ASJ

AF:

0.418

Gnomad EAS

AF:

0.179

Gnomad SAS

AF:

0.295

Gnomad FIN

AF:

0.371

Gnomad MID

AF:

0.468

Gnomad NFE

AF:

0.440

Gnomad OTH

AF:

0.348

GnomAD2 exomes

AF:

0.287

AC:

49740

AN:

173358

AF XY:

0.290

show subpopulations

Gnomad AFR exome

AF:

0.186

Gnomad AMR exome

AF:

0.206

Gnomad ASJ exome

AF:

0.329

Gnomad EAS exome

AF:

0.198

Gnomad FIN exome

AF:

0.301

Gnomad NFE exome

AF:

0.339

Gnomad OTH exome

AF:

0.310

GnomAD4 exome

Data not reliable, filtered out with message: InbreedingCoeff

AF:

0.311

AC:

387665

AN:

1246144

Hom.:

2077

Cov.:

AF XY:

0.310

AC XY:

193995

AN XY:

626200

show subpopulations

Gnomad4 AFR exome

AF:

0.163

AC:

4645

AN:

28532

Gnomad4 AMR exome

AF:

0.191

AC:

7612

AN:

39914

Gnomad4 ASJ exome

AF:

0.316

AC:

7528

AN:

23830

Gnomad4 EAS exome

AF:

0.166

AC:

6036

AN:

36440

Gnomad4 SAS exome

AF:

0.251

AC:

19382

AN:

77362

Gnomad4 FIN exome

AF:

0.284

AC:

12296

AN:

43308

Gnomad4 NFE exome

AF:

0.333

AC:

312791

AN:

939046

Gnomad4 Remaining exome

AF:

0.301

AC:

15880

AN:

52758

Heterozygous variant carriers

11956

23913

35869

47826

59782

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Exome Het

Exome Hom

Variant carriers

11246

22492

33738

44984

56230

<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:

0.334

AC:

47764

AN:

143188

Hom.:

8679

Cov.:

AF XY:

0.328

AC XY:

22755

AN XY:

69382

show subpopulations

Gnomad4 AFR

AF:

0.175

AC:

0.174604

AN:

0.174604

Gnomad4 AMR

AF:

0.287

AC:

0.287073

AN:

0.287073

Gnomad4 ASJ

AF:

0.418

AC:

0.417609

AN:

0.417609

Gnomad4 EAS

AF:

0.180

AC:

0.179545

AN:

0.179545

Gnomad4 SAS

AF:

0.296

AC:

0.296444

AN:

0.296444

Gnomad4 FIN

AF:

0.371

AC:

0.371402

AN:

0.371402

Gnomad4 NFE

AF:

0.440

AC:

0.44024

AN:

0.44024

Gnomad4 OTH

AF:

0.346

AC:

0.345566

AN:

0.345566

Heterozygous variant carriers

1437

2874

4312

5749

7186

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Genome Het

Genome Hom

Variant carriers

476

952

1428

1904

2380

<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:

0.235

Hom.:

495

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Aug 10, 2019

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

Mutation Taster

=99/1

polymorphism (auto)

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