2-227237970-T-TTGTG
Variant summary
Our verdict is Pathogenic. Variant got 18 ACMG points: 18P and 0B. PVS1PM2PP5_Very_Strong
The NM_000091.5(COL4A3):c.92_95dupGTGT(p.Lys34LeufsTer2) variant causes a frameshift change. The variant allele was found at a frequency of 0.00000275 in 1,457,146 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Pathogenic (★★).
Frequency
Consequence
NM_000091.5 frameshift
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Pathogenic. Variant got 18 ACMG points.
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes Cov.: 33
GnomAD3 exomes AF: 0.00000801 AC: 2AN: 249536Hom.: 0 AF XY: 0.00000739 AC XY: 1AN XY: 135380
GnomAD4 exome AF: 0.00000275 AC: 4AN: 1457146Hom.: 0 Cov.: 27 AF XY: 0.00000414 AC XY: 3AN XY: 725234
GnomAD4 genome Cov.: 33
ClinVar
Submissions by phenotype
not provided Pathogenic:1
For these reasons, this variant has been classified as Pathogenic. This premature translational stop signal has been observed in individual(s) with clinical features of Alport syndrome and thin basement membrane nephropathy (PMID: 25307543). This variant is present in population databases (no rsID available, gnomAD 0.003%). This sequence change creates a premature translational stop signal (p.Lys34Leufs*2) in the COL4A3 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in COL4A3 are known to be pathogenic (PMID: 8956999, 24854265, 26809805, 27281700). -
Alport syndrome Pathogenic:1
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Benign familial hematuria;C4746745:Autosomal recessive Alport syndrome;C5882663:Autosomal dominant Alport syndrome Pathogenic:1
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Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at