rs120074159
Variant summary
Our verdict is Pathogenic. Variant got 11 ACMG points: 11P and 0B. PVS1PM2PP5
The NM_025074.7(FRAS1):c.4271C>G(p.Ser1424Ter) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Pathogenic (no stars). Variant results in nonsense mediated mRNA decay.
Frequency
Genomes: not found (cov: 32)
Consequence
FRAS1
NM_025074.7 stop_gained
NM_025074.7 stop_gained
Scores
2
3
2
Clinical Significance
Conservation
PhyloP100: 1.34
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 11 ACMG points.
PVS1
?
Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
PM2
?
Very rare variant in population databases, with high coverage;
PP5
?
Variant 4-78407804-C-G is Pathogenic according to our data. Variant chr4-78407804-C-G is described in ClinVar as [Pathogenic]. Clinvar id is 2813.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.4271C>G | p.Ser1424Ter | stop_gained | 31/74 | ENST00000512123.4 | |
FRAS1 | NM_001166133.2 | c.4271C>G | p.Ser1424Ter | stop_gained | 31/42 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
FRAS1 | ENST00000512123.4 | c.4271C>G | p.Ser1424Ter | stop_gained | 31/74 | 5 | NM_025074.7 | P1 | |
FRAS1 | ENST00000325942.11 | c.4271C>G | p.Ser1424Ter | stop_gained | 31/42 | 1 | |||
FRAS1 | ENST00000682513.1 | c.4271C>G | p.Ser1424Ter | stop_gained | 31/64 | ||||
FRAS1 | ENST00000684159.1 | c.4271C>G | p.Ser1424Ter | stop_gained | 31/45 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD3 genomes
?
Cov.:
32
GnomAD4 exome Cov.: 31
GnomAD4 exome
Cov.:
31
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 | literature only | OMIM | Jun 01, 2003 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
Cadd
Pathogenic
Dann
Uncertain
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Benign
D
MutationTaster
Benign
A;A
Vest4
GERP RS
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at