rs368465318
Variant summary
Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM1PP3_Moderate
The ENST00000205557.12(ABCC6):c.2943G>T(p.Gln981His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000013 in 1,611,422 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 (★★). Synonymous variant affecting the same amino acid position (i.e. Q981Q) has been classified as Likely benign.
Frequency
Consequence
ENST00000205557.12 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 4 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
ABCC6 | NM_001171.6 | c.2943G>T | p.Gln981His | missense_variant | 22/31 | ENST00000205557.12 | NP_001162.5 | |
ABCC6 | NM_001351800.1 | c.2601G>T | p.Gln867His | missense_variant | 22/31 | NP_001338729.1 | ||
ABCC6 | NR_147784.1 | n.2805G>T | non_coding_transcript_exon_variant | 21/29 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
ABCC6 | ENST00000205557.12 | c.2943G>T | p.Gln981His | missense_variant | 22/31 | 1 | NM_001171.6 | ENSP00000205557 | P1 | |
ABCC6 | ENST00000622290.5 | c.2943G>T | p.Gln981His | missense_variant, NMD_transcript_variant | 22/32 | 5 | ENSP00000483331 | |||
ABCC6 | ENST00000456970.6 | c.*152G>T | 3_prime_UTR_variant, NMD_transcript_variant | 21/29 | 2 | ENSP00000405002 |
Frequencies
GnomAD3 genomes AF: 0.0000197 AC: 3AN: 152236Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000572 AC: 14AN: 244840Hom.: 0 AF XY: 0.0000599 AC XY: 8AN XY: 133496
GnomAD4 exome AF: 0.0000123 AC: 18AN: 1459186Hom.: 0 Cov.: 33 AF XY: 0.0000138 AC XY: 10AN XY: 725878
GnomAD4 genome AF: 0.0000197 AC: 3AN: 152236Hom.: 0 Cov.: 33 AF XY: 0.0000269 AC XY: 2AN XY: 74376
ClinVar
Submissions by phenotype
Autosomal recessive inherited pseudoxanthoma elasticum Uncertain:1
Uncertain significance, criteria provided, single submitter | research | PXE International | Feb 16, 2021 | - - |
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Sep 27, 2022 | This sequence change replaces glutamine, which is neutral and polar, with histidine, which is basic and polar, at codon 981 of the ABCC6 protein (p.Gln981His). This variant is present in population databases (rs368465318, gnomAD 0.07%). This missense change has been observed in individual(s) with pseudoxanthoma elasticum (PMID: 18157818). ClinVar contains an entry for this variant (Variation ID: 433434). 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) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on 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. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at