16-16150204-C-T
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM1
The NM_001171.6(ABCC6):c.4441G>A(p.Gly1481Ser) variant causes a missense change. The variant allele was found at a frequency of 0.0000434 in 1,613,884 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★★).
Frequency
Consequence
NM_001171.6 missense
Scores
Clinical Significance
Conservation
Genome browser will be placed here
ACMG classification
Verdict is Uncertain_significance. Variant got 2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
ABCC6 | NM_001171.6 | c.4441G>A | p.Gly1481Ser | missense_variant | Exon 31 of 31 | ENST00000205557.12 | NP_001162.5 | |
ABCC6 | NM_001351800.1 | c.4099G>A | p.Gly1367Ser | missense_variant | Exon 31 of 31 | NP_001338729.1 | ||
ABCC6 | NR_147784.1 | n.4103G>A | non_coding_transcript_exon_variant | Exon 29 of 29 |
Ensembl
Frequencies
GnomAD3 genomes AF: 0.0000394 AC: 6AN: 152214Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000599 AC: 15AN: 250314Hom.: 0 AF XY: 0.0000664 AC XY: 9AN XY: 135596
GnomAD4 exome AF: 0.0000438 AC: 64AN: 1461670Hom.: 0 Cov.: 30 AF XY: 0.0000536 AC XY: 39AN XY: 727134
GnomAD4 genome AF: 0.0000394 AC: 6AN: 152214Hom.: 0 Cov.: 32 AF XY: 0.0000269 AC XY: 2AN XY: 74366
ClinVar
Submissions by phenotype
Autosomal recessive inherited pseudoxanthoma elasticum Uncertain:2
- -
- -
not provided Uncertain:2
- -
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. Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The serine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. ClinVar contains an entry for this variant (Variation ID: 433295). This missense change has been observed in individual(s) with pseudoxanthoma elasticum (PMID: 17617515). This variant is present in population databases (rs63751279, gnomAD 0.02%). This sequence change replaces glycine, which is neutral and non-polar, with serine, which is neutral and polar, at codon 1481 of the ABCC6 protein (p.Gly1481Ser). -
ABCC6-related disorder Uncertain:1
The ABCC6 c.4441G>A variant is predicted to result in the amino acid substitution p.Gly1481Ser. This variant was reported in two individuals with pseudoxanthoma elasticum, although pathogenicity was not established (Pfendner et al. 2007. PubMed ID: 17617515; Table S2, Zheng et al. 2018. PubMed ID: 30056620). This variant is reported in 0.023% of alleles in individuals of South Asian descent in gnomAD. At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. -
Autosomal recessive inherited pseudoxanthoma elasticum;C1867450:Pseudoxanthoma elasticum, forme fruste;C3276161:Arterial calcification, generalized, of infancy, 2 Uncertain:1
- -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at