16-16203406-TCA-T
Variant summary
Our verdict is Pathogenic. Variant got 14 ACMG points: 14P and 0B. PVS1_ModeratePM2PP3_ModeratePP5_Very_Strong
The NM_001171.6(ABCC6):c.998+2_998+3del variant causes a splice donor, splice donor region, intron change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000197 in 152,086 control chromosomes in the GnomAD database, with no homozygous occurrence. 1/1 splice prediction tools predicting alterations to normal splicing. Variant has been reported in ClinVar as Likely pathogenic (★★).
Frequency
Consequence
NM_001171.6 splice_donor, splice_donor_region, intron
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Pathogenic. Variant got 14 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ABCC6 | NM_001171.6 | c.998+2_998+3del | splice_donor_variant, splice_donor_region_variant, intron_variant | ENST00000205557.12 | |||
ABCC6 | NM_001351800.1 | c.656+2_656+3del | splice_donor_variant, splice_donor_region_variant, intron_variant | ||||
ABCC6 | NR_147784.1 | n.1035+2_1035+3del | splice_donor_variant, splice_donor_region_variant, intron_variant, non_coding_transcript_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ABCC6 | ENST00000205557.12 | c.998+2_998+3del | splice_donor_variant, splice_donor_region_variant, intron_variant | 1 | NM_001171.6 | P1 |
Frequencies
GnomAD3 genomes AF: 0.0000197 AC: 3AN: 152086Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.00000399 AC: 1AN: 250752Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 135556
GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.0000363 AC: 53AN: 1461666Hom.: 0 AF XY: 0.0000330 AC XY: 24AN XY: 727142
GnomAD4 genome AF: 0.0000197 AC: 3AN: 152086Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 74274
ClinVar
Submissions by phenotype
Autosomal recessive inherited pseudoxanthoma elasticum Pathogenic:1
Likely pathogenic, no assertion criteria provided | research | PXE International | Mar 02, 2021 | - - |
ABCC6-related disorder Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Jul 31, 2023 | The ABCC6 c.998+2_998+3delTG variant is predicted to result in a deletion affecting a canonical splice site. This variant has been reported in individuals with pseudoxanthoma elasticum and in at least one individual it was reported in the compound heterozygous state (reported as IVS8+2delTG in Chassaing et al. 2005. PubMed ID: 15894595; Table S1, Saeidian et al. 2021. PubMed ID: 34906475). This variant is reported in 0.00088% of alleles in individuals of European (Non-Finnish) descent in gnomAD (http://gnomad.broadinstitute.org/variant/16-16297263-TCA-T). Variants that disrupt the canonical splice donor site are expected to be pathogenic. This variant is interpreted as pathogenic. - |
Autosomal recessive inherited pseudoxanthoma elasticum;C1867450:Pseudoxanthoma elasticum, forme fruste;C3276161:Arterial calcification, generalized, of infancy, 2 Pathogenic:1
Likely pathogenic, criteria provided, single submitter | clinical testing | Fulgent Genetics, Fulgent Genetics | Oct 05, 2021 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at