10-27169929-T-C
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Variant summary
Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2
The NM_001172303.3(MASTL):c.985-15T>C variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000409 in 1,613,604 control chromosomes in the GnomAD database, including 8 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).
Frequency
Genomes: 𝑓 0.00027 ( 2 hom., cov: 32)
Exomes 𝑓: 0.00042 ( 6 hom. )
Consequence
MASTL
NM_001172303.3 splice_polypyrimidine_tract, intron
NM_001172303.3 splice_polypyrimidine_tract, intron
Scores
2
Clinical Significance
Conservation
PhyloP100: 1.12
Genes affected
MASTL (HGNC:19042): (microtubule associated serine/threonine kinase like) This gene encodes a microtubule-associated serine/threonine kinase. Mutations at this locus have been associated with autosomal dominant thrombocytopenia, also known as thrombocytopenia-2. Alternatively spliced transcript variants have been described for this locus. [provided by RefSeq, Feb 2010]
ACBD5 (HGNC:23338): (acyl-CoA binding domain containing 5) This gene encodes a member of the acyl-Coenzyme A binding protein family, known to function in the transport and distribution of long chain acyl-Coenzyme A in cells. This gene may play a role in the differentiation of megakaryocytes and formation of platelets. A related protein in yeast is involved in autophagy of peroxisomes. A mutation in this gene has been associated with autosomal dominant thrombocytopenia. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jul 2014]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -10 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.83).
BP6
Variant 10-27169929-T-C is Benign according to our data. Variant chr10-27169929-T-C is described in ClinVar as [Benign]. Clinvar id is 299790.Status of the report is criteria_provided_single_submitter, 1 stars.
BS2
High AC in GnomAd4 at 41 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
MASTL | NM_001172303.3 | c.985-15T>C | splice_polypyrimidine_tract_variant, intron_variant | ENST00000375940.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MASTL | ENST00000375940.9 | c.985-15T>C | splice_polypyrimidine_tract_variant, intron_variant | 1 | NM_001172303.3 | P5 |
Frequencies
GnomAD3 genomes AF: 0.000269 AC: 41AN: 152134Hom.: 2 Cov.: 32
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GnomAD3 exomes AF: 0.000780 AC: 194AN: 248708Hom.: 3 AF XY: 0.00105 AC XY: 142AN XY: 134948
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GnomAD4 exome AF: 0.000424 AC: 619AN: 1461352Hom.: 6 Cov.: 32 AF XY: 0.000618 AC XY: 449AN XY: 726956
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GnomAD4 genome AF: 0.000269 AC: 41AN: 152252Hom.: 2 Cov.: 32 AF XY: 0.000416 AC XY: 31AN XY: 74444
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ClinVar
Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Thrombocytopenia Benign:1
Benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jan 12, 2018 | This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. - |
Computational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
RBP_binding_hub_radar
RBP_regulation_power_radar
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at