rs63751111
Variant summary
Our verdict is Pathogenic. The variant received 10 ACMG points: 10P and 0B. PM1PM2PP3_StrongPP5_Moderate
The NM_001171.6(ABCC6):c.4041G>C(p.Gln1347His) variant causes a missense, splice region change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,460,506 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. 3/3 splice prediction tools predicting alterations to normal splicing. Variant has been reported in ClinVar as Pathogenic (★). Synonymous variant affecting the same amino acid position (i.e. Q1347Q) has been classified as Pathogenic.
Frequency
Consequence
NM_001171.6 missense, splice_region
Scores
Clinical Significance
Conservation
Publications
- arterial calcification, generalized, of infancy, 2Inheritance: AR Classification: DEFINITIVE Submitted by: G2P
- autosomal recessive inherited pseudoxanthoma elasticumInheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Laboratory for Molecular Medicine, Orphanet, Labcorp Genetics (formerly Invitae), G2P
- arterial calcification of infancyInheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
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ACMG classification
Our verdict: Pathogenic. The variant received 10 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
ABCC6 | NM_001171.6 | c.4041G>C | p.Gln1347His | missense_variant, splice_region_variant | Exon 28 of 31 | ENST00000205557.12 | NP_001162.5 |
Ensembl
Frequencies
GnomAD3 genomes Cov.: 31
GnomAD4 exome AF: 6.85e-7 AC: 1AN: 1460506Hom.: 0 Cov.: 32 AF XY: 0.00000138 AC XY: 1AN XY: 726434 show subpopulations
GnomAD4 genome Cov.: 31
ClinVar
Submissions by phenotype
Autosomal recessive inherited pseudoxanthoma elasticum Pathogenic:1
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Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at