19-12841023-T-TC
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_014975.3(MAST1):c.210dupC(p.Asn71GlnfsTer167) variant causes a frameshift change. The variant allele was found at a frequency of 0.00000202 in 1,485,358 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★★). Variant results in nonsense mediated mRNA decay.
Frequency
Consequence
NM_014975.3 frameshift
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 2 ACMG points.
Transcripts
RefSeq
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
MAST1 | ENST00000251472.9 | c.210dupC | p.Asn71GlnfsTer167 | frameshift_variant | Exon 3 of 26 | 1 | NM_014975.3 | ENSP00000251472.3 | ||
MAST1 | ENST00000591495.6 | c.198dupC | p.Asn67GlnfsTer167 | frameshift_variant | Exon 4 of 13 | 5 | ENSP00000466470.1 | |||
MAST1 | ENST00000590883.1 | n.310dupC | non_coding_transcript_exon_variant | Exon 3 of 6 | 5 | |||||
HOOK2 | ENST00000589765.1 | n.33-14524dupG | intron_variant | Intron 1 of 3 | 5 |
Frequencies
GnomAD3 genomes AF: 0.00000661 AC: 1AN: 151258Hom.: 0 Cov.: 32
GnomAD4 exome AF: 0.00000150 AC: 2AN: 1334100Hom.: 0 Cov.: 26 AF XY: 0.00000149 AC XY: 1AN XY: 669368
GnomAD4 genome AF: 0.00000661 AC: 1AN: 151258Hom.: 0 Cov.: 32 AF XY: 0.0000136 AC XY: 1AN XY: 73800
ClinVar
Submissions by phenotype
Mega-corpus-callosum syndrome with cerebellar hypoplasia and cortical malformations Uncertain:1
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not provided Uncertain:1
In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. ClinVar contains an entry for this variant (Variation ID: 690392). This variant has not been reported in the literature in individuals affected with MAST1-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Asn71Glnfs*167) in the MAST1 gene. It is expected to result in an absent or disrupted protein product. However, the current clinical and genetic evidence is not sufficient to establish whether loss-of-function variants in MAST1 cause disease. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at