rs72664236
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Variant summary
Our verdict is Likely pathogenic. Variant got 9 ACMG points: 9P and 0B. PVS1PP5
The NM_001171.6(ABCC6):c.3912del(p.Lys1305SerfsTer54) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000637 in 1,413,322 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: 0.0000064 ( 0 hom. )
Consequence
ABCC6
NM_001171.6 frameshift
NM_001171.6 frameshift
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: -0.0130
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 Likely_pathogenic. Variant got 9 ACMG points.
PVS1
?
Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
PP5
?
Variant 16-16155001-TC-T is Pathogenic according to our data. Variant chr16-16155001-TC-T is described in ClinVar as [Likely_pathogenic]. Clinvar id is 433336.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr16-16155001-TC-T is described in Lovd as [Pathogenic].
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ABCC6 | NM_001171.6 | c.3912del | p.Lys1305SerfsTer54 | frameshift_variant | 28/31 | ENST00000205557.12 | |
ABCC6 | NM_001351800.1 | c.3570del | p.Lys1191SerfsTer54 | frameshift_variant | 28/31 | ||
ABCC6 | NR_147784.1 | n.3574del | non_coding_transcript_exon_variant | 26/29 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ABCC6 | ENST00000205557.12 | c.3912del | p.Lys1305SerfsTer54 | frameshift_variant | 28/31 | 1 | NM_001171.6 | P1 | |
ABCC6 | ENST00000576204.6 | n.775del | non_coding_transcript_exon_variant | 1/2 | 5 | ||||
ABCC6 | ENST00000456970.6 | c.*921del | 3_prime_UTR_variant, NMD_transcript_variant | 26/29 | 2 | ||||
ABCC6 | ENST00000622290.5 | c.*84del | 3_prime_UTR_variant, NMD_transcript_variant | 29/32 | 5 |
Frequencies
GnomAD3 genomes ? Cov.: 31
GnomAD3 genomes
?
Cov.:
31
GnomAD4 exome AF: 0.00000637 AC: 9AN: 1413322Hom.: 0 Cov.: 32 AF XY: 0.00000716 AC XY: 5AN XY: 698716
GnomAD4 exome
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GnomAD4 genome ? Cov.: 31
GnomAD4 genome
?
Cov.:
31
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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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at