1-197084431-T-TA

Position:

• chr1-197084431-T-TA

Variant summary

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

The NM_018136.5(ASPM):​c.10332-6_10332-5insT variant causes a splice region, splice polypyrimidine tract, 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, splice_polypyrimidine_tract, intron
• Clinical Significance: 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-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/exons	MANE	Protein	UniProt
ASPM	NM_018136.5	c.10332-6_10332-5insT		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		ENST00000367409.9	NP_060606.3
ASPM	NM_001206846.2	c.5577-6_5577-5insT		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant			NP_001193775.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ASPM	ENST00000367409.9	c.10332-6_10332-5insT		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		1	NM_018136.5	ENSP00000356379	P1

Frequencies

GnomAD3 genomes AF: 0.334 AC: 47758 AN: 143130 Hom.: 8683 Cov.: 0

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

GnomAD4 exome Data not reliable, filtered out with message: InbreedingCoeff AF: 0.311 AC: 387665 AN: 1246144 Hom.: 2077 Cov.: 0 AF XY: 0.310 AC XY: 193995 AN XY: 626200

Gnomad4 AFR exome AF: 0.163

Gnomad4 AMR exome AF: 0.191

Gnomad4 ASJ exome AF: 0.316

Gnomad4 EAS exome AF: 0.166

Gnomad4 SAS exome AF: 0.251

Gnomad4 FIN exome AF: 0.284

Gnomad4 NFE exome AF: 0.333

Gnomad4 OTH exome AF: 0.301

GnomAD4 genome AF: 0.334 AC: 47764 AN: 143188 Hom.: 8679 Cov.: 0 AF XY: 0.328 AC XY: 22755 AN XY: 69382

Gnomad4 AFR AF: 0.175

Gnomad4 AMR AF: 0.287

Gnomad4 ASJ AF: 0.418

Gnomad4 EAS AF: 0.180

Gnomad4 SAS AF: 0.296

Gnomad4 FIN AF: 0.371

Gnomad4 NFE AF: 0.440

Gnomad4 OTH AF: 0.346

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

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)		0.0		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

Other links and lift over

dbSNP: rs200839523; hg19: chr1-197053561;