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GeneBe

1-197084420-CT-C

Variant summary

Our verdict is Uncertain significance. Variant got 5 ACMG points: 5P and 0B. PM2_SupportingPM4PP5_Moderate

The NM_018136.5(ASPM):c.10337del(p.Lys3446SerfsTer6) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD Genomes project. Variant has been reported in ClinVar as Likely pathogenic (★).

Frequency

Genomes: not found (cov: 31)

Consequence

ASPM
NM_018136.5 frameshift

Scores

Not classified

Clinical Significance

Likely pathogenic criteria provided, single submitter P:1

Conservation

PhyloP100: 2.97

Links

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 5 ACMG points.

PM2
?
Very rare variant; Number of alleles below threshold, Median coverage is 31.
PM4
?
Frameshift in the end of transcript resulting in stoplost. Downstream stopcodon found after 3456 codons.
PP5
?
Variant 1-197084420-CT-C is Pathogenic according to our data. Variant chr1-197084420-CT-C is described in ClinVar as [Likely_pathogenic]. Clinvar id is 503777.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
ASPMNM_018136.5 linkuse as main transcriptc.10337del p.Lys3446SerfsTer6 frameshift_variant 28/28 ENST00000367409.9
ASPMNM_001206846.2 linkuse as main transcriptc.5582del p.Lys1861SerfsTer6 frameshift_variant 27/27

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
ASPMENST00000367409.9 linkuse as main transcriptc.10337del p.Lys3446SerfsTer6 frameshift_variant 28/281 NM_018136.5 P1Q8IZT6-1

Frequencies

GnomAD3 genomes
Cov.:
31
GnomAD4 exome
AF:
0.00000346
AC:
5
AN:
1446656
Hom.:
0
AF XY:
0.00000278
AC XY:
2
AN XY:
720422
show subpopulations
Gnomad4 AFR exome
AF:
0.00
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:
0.00
Gnomad4 NFE exome
AF:
0.00000454
Gnomad4 OTH exome
AF:
0.00

ClinVar

Significance: Likely pathogenic
Submissions summary: Pathogenic:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Pathogenic:1
Likely pathogenic, criteria provided, single submitterclinical testingGeneDxOct 04, 2017The c.10337delA variant in the ASPM gene has not been reported previously as a pathogenic variant nor as a benign variant, to our knowledge. It is not observed in large population cohorts (Lek et al., 2016). The c.10337delA variant causes a frameshift starting with codon Lysine 3446, changes this amino acid to a Serine residue, and creates a premature Stop codon at position 6 of the new reading frame, denoted p.Lys3446SerfsX6. This variant is predicted to cause loss of normal protein function through protein truncation as 32 amino acids of the protein are replaced with 5 incorrect amino acids. Therefore, this variant is likely pathogenic; however, the possibility that it is benign cannot becompletely excluded. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction

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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs1553325275; hg19: chr1-197053550; API