16-16150197-G-T
Variant summary
Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM1PP3_Moderate
The ENST00000205557.12(ABCC6):c.4448C>A(p.Pro1483Gln) variant causes a missense change. The variant allele was found at a frequency of 0.00000496 in 1,613,590 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 Uncertain significance (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P1483L) has been classified as Uncertain significance.
Frequency
Consequence
ENST00000205557.12 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 4 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
ABCC6 | NM_001171.6 | c.4448C>A | p.Pro1483Gln | missense_variant | 31/31 | ENST00000205557.12 | NP_001162.5 | |
ABCC6 | NM_001351800.1 | c.4106C>A | p.Pro1369Gln | missense_variant | 31/31 | NP_001338729.1 | ||
ABCC6 | NR_147784.1 | n.4110C>A | non_coding_transcript_exon_variant | 29/29 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
ABCC6 | ENST00000205557.12 | c.4448C>A | p.Pro1483Gln | missense_variant | 31/31 | 1 | NM_001171.6 | ENSP00000205557 | P1 | |
ABCC6 | ENST00000456970.6 | c.*1457C>A | 3_prime_UTR_variant, NMD_transcript_variant | 29/29 | 2 | ENSP00000405002 | ||||
ABCC6 | ENST00000622290.5 | c.*620C>A | 3_prime_UTR_variant, NMD_transcript_variant | 32/32 | 5 | ENSP00000483331 |
Frequencies
GnomAD3 genomes AF: 0.0000131 AC: 2AN: 152200Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000160 AC: 4AN: 249486Hom.: 0 AF XY: 0.0000148 AC XY: 2AN XY: 135378
GnomAD4 exome AF: 0.00000411 AC: 6AN: 1461390Hom.: 0 Cov.: 30 AF XY: 0.00000275 AC XY: 2AN XY: 727006
GnomAD4 genome AF: 0.0000131 AC: 2AN: 152200Hom.: 0 Cov.: 33 AF XY: 0.0000134 AC XY: 1AN XY: 74352
ClinVar
Submissions by phenotype
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | May 30, 2022 | This sequence change replaces proline, which is neutral and non-polar, with glutamine, which is neutral and polar, at codon 1483 of the ABCC6 protein (p.Pro1483Gln). This variant is present in population databases (no rsID available, gnomAD 0.01%). This variant has not been reported in the literature in individuals affected with ABCC6-related conditions. ClinVar contains an entry for this variant (Variation ID: 1484716). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt ABCC6 protein function. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. - |
Autosomal recessive inherited pseudoxanthoma elasticum;C1867450:Pseudoxanthoma elasticum, forme fruste;C3276161:Arterial calcification, generalized, of infancy, 2 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Fulgent Genetics, Fulgent Genetics | Apr 01, 2022 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at