16-16190308-G-T
Variant summary
Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM1PP3_Strong
The NM_001171.6(ABCC6):c.1491C>A(p.Asn497Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000372 in 1,614,056 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 (★★).
Frequency
Consequence
NM_001171.6 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_pathogenic. Variant got 6 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
ABCC6 | NM_001171.6 | c.1491C>A | p.Asn497Lys | missense_variant | Exon 12 of 31 | ENST00000205557.12 | NP_001162.5 | |
ABCC6 | NM_001351800.1 | c.1149C>A | p.Asn383Lys | missense_variant | Exon 12 of 31 | NP_001338729.1 | ||
ABCC6 | NR_147784.1 | n.1528C>A | non_coding_transcript_exon_variant | Exon 12 of 29 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
ABCC6 | ENST00000205557.12 | c.1491C>A | p.Asn497Lys | missense_variant | Exon 12 of 31 | 1 | NM_001171.6 | ENSP00000205557.7 | ||
ABCC6 | ENST00000456970.6 | n.1491C>A | non_coding_transcript_exon_variant | Exon 12 of 29 | 2 | ENSP00000405002.2 | ||||
ABCC6 | ENST00000622290.5 | n.1491C>A | non_coding_transcript_exon_variant | Exon 12 of 32 | 5 | ENSP00000483331.2 |
Frequencies
GnomAD3 genomes AF: 0.0000197 AC: 3AN: 152172Hom.: 0 Cov.: 31
GnomAD3 exomes AF: 0.00000795 AC: 2AN: 251418Hom.: 0 AF XY: 0.00000736 AC XY: 1AN XY: 135884
GnomAD4 exome AF: 0.00000205 AC: 3AN: 1461884Hom.: 0 Cov.: 35 AF XY: 0.00000275 AC XY: 2AN XY: 727238
GnomAD4 genome AF: 0.0000197 AC: 3AN: 152172Hom.: 0 Cov.: 31 AF XY: 0.0000269 AC XY: 2AN XY: 74320
ClinVar
Submissions by phenotype
Autosomal recessive inherited pseudoxanthoma elasticum Uncertain:1
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not provided Uncertain:1
This sequence change replaces asparagine, which is neutral and polar, with lysine, which is basic and polar, at codon 497 of the ABCC6 protein (p.Asn497Lys). This variant is present in population databases (rs72653770, gnomAD 0.006%). This missense change has been observed in individual(s) with clinical features of ABCC6-related conditions (PMID: 11536079, 16835894). This variant is also known as 1489C>A. ClinVar contains an entry for this variant (Variation ID: 433234). 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 not 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
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Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at