rs1343632105
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Variant summary
Our verdict is Pathogenic. Variant got 11 ACMG points: 11P and 0B. PVS1PM2PP5
The NM_001171.6(ABCC6):c.709_710insCT(p.Trp237SerfsTer22) variant causes a frameshift change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Likely pathogenic (no stars). Variant results in nonsense mediated mRNA decay.
Frequency
Genomes: not found (cov: 31)
Exomes 𝑓: 0.0000014 ( 0 hom. )
Failed GnomAD Quality Control
Consequence
ABCC6
NM_001171.6 frameshift
NM_001171.6 frameshift
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 6.49
Genes affected
ABCC6 (HGNC:57): (ATP binding cassette subfamily C member 6) The protein encoded by this gene is a member of the superfamily of ATP-binding cassette (ABC) transporters. ABC proteins transport various molecules across extra- and intra-cellular membranes. ABC genes are divided into seven distinct subfamilies (ABC1, MDR/TAP, MRP, ALD, OABP, GCN20, White). The encoded protein, a member of the MRP subfamily, is involved in multi-drug resistance. Mutations in this gene cause pseudoxanthoma elasticum. Alternatively spliced transcript variants that encode different proteins have been described for this gene. [provided by RefSeq, Jul 2008]
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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 16-16208812-C-CAG is Pathogenic according to our data. Variant chr16-16208812-C-CAG is described in ClinVar as [Likely_pathogenic]. Clinvar id is 433436.Status of the report is no_assertion_criteria_provided, 0 stars.
Transcripts
RefSeq
| Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
|---|---|---|---|---|---|---|---|
| ABCC6 | NM_001171.6 | c.709_710insCT | p.Trp237SerfsTer22 | frameshift_variant | 7/31 | ENST00000205557.12 | |
| ABCC6 | NM_001351800.1 | c.367_368insCT | p.Trp123SerfsTer22 | frameshift_variant | 7/31 | ||
| ABCC6 | NR_147784.1 | n.746_747insCT | non_coding_transcript_exon_variant | 7/29 | |||
| LOC105371100 | XR_933131.3 | upstream_gene_variant |
Ensembl
| Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
|---|---|---|---|---|---|---|---|---|---|
| ABCC6 | ENST00000205557.12 | c.709_710insCT | p.Trp237SerfsTer22 | frameshift_variant | 7/31 | 1 | NM_001171.6 | P1 |
Frequencies
GnomAD3 genomes ? Cov.: 31
GnomAD3 genomes
?
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31
GnomAD3 exomes AF: 0.00000400 AC: 1AN: 249948Hom.: 0 AF XY: 0.00000739 AC XY: 1AN XY: 135372
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GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00000137 AC: 2AN: 1461640Hom.: 0 Cov.: 33 AF XY: 0.00000138 AC XY: 1AN XY: 727138
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Data not reliable, filtered out with message: AS_VQSR
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GnomAD4 genome ? Cov.: 31
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ClinVar
Significance: Likely pathogenic
Submissions summary: Pathogenic:1
Revision: no assertion criteria provided
LINK: link
Submissions by phenotype
Autosomal recessive inherited pseudoxanthoma elasticum Pathogenic:1
| Likely pathogenic, no assertion criteria provided | research | PXE International | Mar 02, 2021 | - - |
Computational scores
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Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at