chr1-197084431-T-TAA

Variant names:

• chr1-197084431-T-TAA
• rs200839523
• NM_018136.5:c.10332-7_10332-6dupTT

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS1

The NM_018136.5(ASPM):​c.10332-7_10332-6dupTT variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.00051 (0 hom., cov: 0)
  • Exomes 𝑓: 0.0084 (0 hom.)
• Consequence: ASPM NM_018136.5 splice_region, intron
• Clinical Significance: Not reported in ClinVar
• 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 Likely_benign. Variant got -4 ACMG points.

• BS1: Variant frequency is greater than expected in population eas. gnomad4 allele frequency = 0.00051 (73/143272) while in subpopulation EAS AF= 0.00285 (14/4918). AF 95% confidence interval is 0.00172. There are 0 homozygotes in gnomad4. There are 40 alleles in male gnomad4 subpopulation. Median coverage is 0. This position pass quality control queck.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ASPM	NM_018136.5	c.10332-7_10332-6dupTT		splice_region_variant, intron_variant	Intron 27 of 27	ENST00000367409.9	NP_060606.3
ASPM	NM_001206846.2	c.5577-7_5577-6dupTT		splice_region_variant, intron_variant	Intron 26 of 26		NP_001193775.1

Ensembl

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

Frequencies

GnomAD3 genomes AF: 0.000496 AC: 71 AN: 143214 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.0000259

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000280

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00284

Gnomad SAS AF: 0.000664

Gnomad FIN AF: 0.000799

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000625

Gnomad OTH AF: 0.000514

GnomAD4 exome AF: 0.00840 AC: 10593 AN: 1261552 Hom.: 0 Cov.: 0 AF XY: 0.00791 AC XY: 5013 AN XY: 634116

Gnomad4 AFR exome AF: 0.00299

Gnomad4 AMR exome AF: 0.00235

Gnomad4 ASJ exome AF: 0.00495

Gnomad4 EAS exome AF: 0.00637

Gnomad4 SAS exome AF: 0.00330

Gnomad4 FIN exome AF: 0.00409

Gnomad4 NFE exome AF: 0.00972

Gnomad4 OTH exome AF: 0.00666

GnomAD4 genome AF: 0.000510 AC: 73 AN: 143272 Hom.: 0 Cov.: 0 AF XY: 0.000576 AC XY: 40 AN XY: 69412

Gnomad4 AFR AF: 0.0000258

Gnomad4 AMR AF: 0.000280

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00285

Gnomad4 SAS AF: 0.000888

Gnomad4 FIN AF: 0.000799

Gnomad4 NFE AF: 0.000625

Gnomad4 OTH AF: 0.00102

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Splicing

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;