rs886037766
Positions:
Variant summary
Our verdict is Pathogenic. Variant got 12 ACMG points: 12P and 0B. PVS1PM2PP3PP5
The NM_025074.7(FRAS1):c.5664_5665+19delinsT variant causes a splice donor, splice donor 5th base, coding sequence, intron change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Pathogenic (no stars).
Frequency
Genomes: not found (cov: 32)
Consequence
FRAS1
NM_025074.7 splice_donor, splice_donor_5th_base, coding_sequence, intron
NM_025074.7 splice_donor, splice_donor_5th_base, coding_sequence, intron
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 7.73
Genes affected
FRAS1 (HGNC:19185): (Fraser extracellular matrix complex subunit 1) This gene encodes an extracellular matrix protein that appears to function in the regulation of epidermal-basement membrane adhesion and organogenesis during development. Mutations in this gene cause Fraser syndrome, a multisystem malformation that can include craniofacial, urogenital and respiratory system abnormalities. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Oct 2009]
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ACMG classification
Classification made for transcript
Verdict is Pathogenic. Variant got 12 ACMG points.
PVS1
?
Splicing variant, LoF is a know mechanism of disease, No cryptic splice site detected. Exon removal results in frameshift change.
PM2
?
Very rare variant in population databases, with high coverage;
PP3
?
No computational evidence supports a deleterious effect, but strongly conserved according to phyloP
PP5
?
Variant 4-78441296-AGGTACTACTTCCTGTAAAAC-T is Pathogenic according to our data. Variant chr4-78441296-AGGTACTACTTCCTGTAAAAC-T is described in ClinVar as [Pathogenic]. Clinvar id is 219183.Status of the report is no_assertion_criteria_provided, 0 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
FRAS1 | NM_025074.7 | c.5664_5665+19delinsT | splice_donor_variant, splice_donor_5th_base_variant, coding_sequence_variant, intron_variant | 41/74 | ENST00000512123.4 | ||
FRAS1 | NM_001166133.2 | c.5664_5665+19delinsT | splice_donor_variant, splice_donor_5th_base_variant, coding_sequence_variant, intron_variant | 41/42 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
FRAS1 | ENST00000512123.4 | c.5664_5665+19delinsT | splice_donor_variant, splice_donor_5th_base_variant, coding_sequence_variant, intron_variant | 41/74 | 5 | NM_025074.7 | P1 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD3 genomes
?
Cov.:
32
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome ? Cov.: 32
GnomAD4 genome
?
Cov.:
32
ClinVar
Significance: Pathogenic
Submissions summary: Pathogenic:1
Revision: no assertion criteria provided
LINK: link
Submissions by phenotype
Fraser syndrome 1 Pathogenic:1
Pathogenic, no assertion criteria provided | research | Centre for Genomic and Experimental Medicine, University of Edinburgh | - | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at