rs606231127
Variant summary
Our verdict is Pathogenic. Variant got 12 ACMG points: 12P and 0B. PVS1PM2PP5_Moderate
The NM_022369.4(STRA6):c.527_528insG(p.Ser177GlnfsTer58) variant causes a frameshift change. The variant allele was found at a frequency of 0.00000274 in 1,461,276 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Likely pathogenic (★). Variant results in nonsense mediated mRNA decay.
Frequency
Genomes: not found (cov: 32)
Exomes 𝑓: 0.0000027 ( 0 hom. )
Consequence
STRA6
NM_022369.4 frameshift
NM_022369.4 frameshift
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 6.62
Genes affected
STRA6 (HGNC:30650): (signaling receptor and transporter of retinol STRA6) The protein encoded by this gene is a membrane protein involved in the metabolism of retinol. The encoded protein acts as a receptor for retinol/retinol binding protein complexes. This protein removes the retinol from the complex and transports it across the cell membrane. Defects in this gene are a cause of syndromic microphthalmia type 9 (MCOPS9). Several transcript variants encoding a few different isoforms have been found for this gene. [provided by RefSeq, Dec 2008]
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ACMG classification
Classification made for transcript
Verdict is Pathogenic. Variant got 12 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 15-74195371-G-GC is Pathogenic according to our data. Variant chr15-74195371-G-GC is described in ClinVar as [Likely_pathogenic]. Clinvar id is 1140.Status of the report is criteria_provided_single_submitter, 1 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
STRA6 | NM_022369.4 | c.527_528insG | p.Ser177GlnfsTer58 | frameshift_variant | 7/19 | ENST00000395105.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
STRA6 | ENST00000395105.9 | c.527_528insG | p.Ser177GlnfsTer58 | frameshift_variant | 7/19 | 1 | NM_022369.4 | P1 |
Frequencies
GnomAD3 genomes ? Cov.: 32
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GnomAD3 exomes AF: 0.00000800 AC: 2AN: 249998Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 135390
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GnomAD4 exome AF: 0.00000274 AC: 4AN: 1461276Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1AN XY: 726936
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GnomAD4 genome ? Cov.: 32
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ClinVar
Significance: Likely pathogenic
Submissions summary: Pathogenic:2
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Matthew-Wood syndrome Pathogenic:1
Pathogenic, no assertion criteria provided | literature only | OMIM | Jun 01, 2007 | - - |
not provided Pathogenic:1
Likely pathogenic, criteria provided, single submitter | clinical testing | GeneDx | Mar 25, 2019 | The c.527dupG variant in the STRA6 gene has been reported previously as apparently homozygous in a fetus with features of Matthew-Wood syndrome (Golzio et al., 2007). The c.527dupG variant causes a frameshift starting with codon Serine 177, changes this amino acid to a Glutamine residue, and creates a premature Stop codon at position 58 of the new reading frame, denoted p.Ser177GlnfsX58. This variant is predicted to cause loss of normal protein function either through protein truncation or nonsense-mediated mRNA decay. Although not observed as homozygous, the c.527dupG variant is observed in 2/33530 (0.006%) alleles from individuals of Latino background in large population cohorts (Lek et al., 2016). We interpret c.527dupG as a likely pathogenic variant. - |
Computational scores
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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