rs2606921
Variant summary
Our verdict is Benign. Variant got -18 ACMG points: 0P and 18B. BP4_ModerateBP6_Very_StrongBS1BS2
The NM_001171.6(ABCC6):c.473C>T(p.Ala158Val) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0108 in 149,362 control chromosomes in the GnomAD database, including 20 homozygotes. In-silico tool predicts a benign outcome for this variant. 17/23 in silico tools predict a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★★). Synonymous variant affecting the same amino acid position (i.e. A158A) has been classified as Likely benign.
Frequency
Consequence
NM_001171.6 missense, splice_region
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -18 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ABCC6 | NM_001171.6 | c.473C>T | p.Ala158Val | missense_variant, splice_region_variant | 4/31 | ENST00000205557.12 | |
ABCC6 | NM_001351800.1 | c.131C>T | p.Ala44Val | missense_variant, splice_region_variant | 4/31 | ||
ABCC6 | NR_147784.1 | n.510C>T | splice_region_variant, non_coding_transcript_exon_variant | 4/29 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ABCC6 | ENST00000205557.12 | c.473C>T | p.Ala158Val | missense_variant, splice_region_variant | 4/31 | 1 | NM_001171.6 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0108 AC: 1606AN: 149250Hom.: 20 Cov.: 25
GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00145 AC: 2069AN: 1431380Hom.: 53 Cov.: 31 AF XY: 0.00145 AC XY: 1028AN XY: 710286
GnomAD4 genome ? AF: 0.0108 AC: 1607AN: 149362Hom.: 20 Cov.: 25 AF XY: 0.00989 AC XY: 722AN XY: 73012
ClinVar
Submissions by phenotype
Autosomal recessive inherited pseudoxanthoma elasticum Benign:1
Likely benign, no assertion criteria provided | research | PXE International | Feb 02, 2021 | - - |
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | May 28, 2021 | This variant is associated with the following publications: (PMID: 28655553, 31589614, 16392638, 16086317) - |
Autosomal recessive inherited pseudoxanthoma elasticum;C1867450:Pseudoxanthoma elasticum, forme fruste;C3276161:Arterial calcification, generalized, of infancy, 2 Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Fulgent Genetics, Fulgent Genetics | Sep 29, 2021 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at