rs786205471
Variant summary
Our verdict is Pathogenic. Variant got 11 ACMG points: 11P and 0B. PVS1PM2PP5
The NM_031433.4(MFRP):c.746G>A(p.Trp249Ter) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,460,398 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Variant results in nonsense mediated mRNA decay.
Frequency
Consequence
NM_031433.4 stop_gained
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Pathogenic. Variant got 11 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
MFRP | NM_031433.4 | c.746G>A | p.Trp249Ter | stop_gained | 6/15 | ENST00000619721.6 | |
C1QTNF5 | NM_015645.5 | c.-1891G>A | 5_prime_UTR_variant | 6/15 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MFRP | ENST00000619721.6 | c.746G>A | p.Trp249Ter | stop_gained | 6/15 | 1 | NM_031433.4 | P1 | |
MFRP | ENST00000360167.4 | c.746G>A | p.Trp249Ter | stop_gained | 6/10 | 2 | |||
MFRP | ENST00000529147.2 | n.709G>A | non_coding_transcript_exon_variant | 5/6 | 5 | ||||
MFRP | ENST00000634542.1 | downstream_gene_variant | 3 |
Frequencies
GnomAD3 genomes ? Cov.: 33
GnomAD3 exomes AF: 0.00000411 AC: 1AN: 243290Hom.: 0 AF XY: 0.00000756 AC XY: 1AN XY: 132318
GnomAD4 exome AF: 0.00000137 AC: 2AN: 1460398Hom.: 0 Cov.: 34 AF XY: 0.00000138 AC XY: 1AN XY: 726424
GnomAD4 genome ? Cov.: 33
ClinVar
Submissions by phenotype
Isolated microphthalmia 5 Pathogenic:2Uncertain:1
Uncertain significance, criteria provided, single submitter | curation | Department Of Genetics, Sultan Qaboos University Hospital, Sultan Qaboos University | Dec 30, 2017 | - - |
Pathogenic, criteria provided, single submitter | clinical testing | Invitae | Nov 17, 2023 | This sequence change creates a premature translational stop signal (p.Trp249*) in the MFRP gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in MFRP are known to be pathogenic (PMID: 12140190, 15976030, 20361016). This variant is present in population databases (rs786205471, gnomAD 0.0009%). This premature translational stop signal has been observed in individual(s) with retinal dystrophy (PMID: 32996714). ClinVar contains an entry for this variant (Variation ID: 191026). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. For these reasons, this variant has been classified as Pathogenic. - |
Pathogenic, criteria provided, single submitter | research | Center for Genomic Medicine, King Faisal Specialist Hospital and Research Center | Mar 17, 2024 | - - |
not provided Pathogenic:1
Likely pathogenic, criteria provided, single submitter | research | Department Of Translational Genomics (developmental Genetics Section), King Faisal Specialist Hospital & Research Centre | - | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at