chr4-73408735-C-T
Variant summary
Our verdict is Pathogenic. Variant got 16 ACMG points: 16P and 0B. PVS1PP5_Very_Strong
The NM_000477.7(ALB):c.412C>T(p.Arg138*) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000867 in 1,613,896 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 Pathogenic (★★). Variant results in nonsense mediated mRNA decay.
Frequency
Consequence
NM_000477.7 stop_gained
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Pathogenic. Variant got 16 ACMG points.
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes AF: 0.0000263 AC: 4AN: 152142Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.00000398 AC: 1AN: 251278Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 135806
GnomAD4 exome AF: 0.00000684 AC: 10AN: 1461754Hom.: 0 Cov.: 31 AF XY: 0.00000550 AC XY: 4AN XY: 727174
GnomAD4 genome AF: 0.0000263 AC: 4AN: 152142Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1AN XY: 74318
ClinVar
Submissions by phenotype
Analbuminemia Pathogenic:2Other:1
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The p.Arg138X variant in ALB has been reported in 2 homozygous individuals with congenital analbuminemia Watkins 1994, Campagnoli 2005). This variant has also b een identified in 1/66370 of European chromosomes by the Exome Aggregation Conso rtium (ExAC, http://exac.broadinstitute.org; dbSNP rs77238412). Although this v ariant has been seen in the general population, its frequency is low enough to b e consistent with a recessive carrier frequency. This nonsense variant leads to a premature termination codon at position 138, which is predicted to lead to a t runcated or absent protein. In summary, this variant meets our criteria to be cl assified as pathogenic for congenital analbuminemia in an autosomal recessive ma nner based upon reports in affected individuals and predicted functional impact on the protein. -
not provided Pathogenic:1
Nonsense variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss-of-function is a known mechanism of disease; Not observed at significant frequency in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 34662886, 25525159, 7937781, 20415703, 15996651, 15300429, 30609409, 32181025, 32553838) -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at