1-197084431-TA-T

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_018136.5(ASPM):c.10332-6del variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.119 in 1,329,732 control chromosomes in the GnomAD database, including 3 homozygotes. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0035 (2 hom., cov: 0)
  • Exomes 𝑓: 0.13 (1 hom.)
• Consequence: ASPM NM_018136.5 splice_region, splice_polypyrimidine_tract, intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.439

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]

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP6: Variant 1-197084431-TA-T is Benign according to our data. Variant chr1-197084431-TA-T is described in ClinVar as [Likely_benign]. Clinvar id is 1204775.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr1-197084431-TA-T is described in Lovd as [Likely_benign].
• BA1: GnomAdExome4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.256 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ASPM	NM_018136.5	c.10332-6del		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		ENST00000367409.9
ASPM	NM_001206846.2	c.5577-6del		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ASPM	ENST00000367409.9	c.10332-6del		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		1	NM_018136.5	P1

Frequencies

GnomAD3 genomes AF: 0.00350 AC: 500 AN: 143052 Hom.: 2 Cov.: 0

Gnomad AFR AF: 0.00477

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00343

Gnomad ASJ AF: 0.00149

Gnomad EAS AF: 0.00142

Gnomad SAS AF: 0.000885

Gnomad FIN AF: 0.0149

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00180

Gnomad OTH AF: 0.00155

GnomAD4 exome AF: 0.133 AC: 157885 AN: 1186624 Hom.: 1 Cov.: 0 AF XY: 0.135 AC XY: 80485 AN XY: 594382

Gnomad4 AFR exome AF: 0.241

Gnomad4 AMR exome AF: 0.252

Gnomad4 ASJ exome AF: 0.142

Gnomad4 EAS exome AF: 0.261

Gnomad4 SAS exome AF: 0.189

Gnomad4 FIN exome AF: 0.149

Gnomad4 NFE exome AF: 0.115

Gnomad4 OTH exome AF: 0.143

GnomAD4 genome AF: 0.00352 AC: 504 AN: 143108 Hom.: 2 Cov.: 0 AF XY: 0.00394 AC XY: 273 AN XY: 69298

Gnomad4 AFR AF: 0.00483

Gnomad4 AMR AF: 0.00350

Gnomad4 ASJ AF: 0.00149

Gnomad4 EAS AF: 0.00142

Gnomad4 SAS AF: 0.000889

Gnomad4 FIN AF: 0.0149

Gnomad4 NFE AF: 0.00180

Gnomad4 OTH AF: 0.00153

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Aug 10, 2019

- -

Computational scores

Source: dbNSFP v4.3

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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

Other links and lift over

dbSNP: rs200839523; hg19: chr1-197053561;