13-52024851-TAAAC-T
Variant summary
Our verdict is Pathogenic. Variant got 12 ACMG points: 12P and 0B. PVS1PM2PP5_Moderate
The NM_001004127.3(ALG11):c.1123_1126delAACA(p.Asn375PhefsTer6) variant causes a frameshift change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,676 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Pathogenic (★). Variant results in nonsense mediated mRNA decay.
Frequency
Consequence
NM_001004127.3 frameshift
Scores
Clinical Significance
Conservation
Genome browser will be placed here
ACMG classification
Verdict is Pathogenic. Variant got 12 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
ALG11 | NM_001004127.3 | c.1123_1126delAACA | p.Asn375PhefsTer6 | frameshift_variant | Exon 3 of 4 | ENST00000521508.2 | NP_001004127.2 | |
UTP14C | NM_021645.6 | c.-571_-568delAACA | 5_prime_UTR_variant | Exon 1 of 2 | ENST00000521776.2 | NP_067677.4 | ||
ALG11 | NR_036571.3 | n.66-3466_66-3463delAACA | intron_variant | Intron 1 of 1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
ALG11 | ENST00000521508.2 | c.1123_1126delAACA | p.Asn375PhefsTer6 | frameshift_variant | Exon 3 of 4 | 1 | NM_001004127.3 | ENSP00000430236.1 | ||
UTP14C | ENST00000521776 | c.-571_-568delAACA | 5_prime_UTR_variant | Exon 1 of 2 | 1 | NM_021645.6 | ENSP00000428619.1 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD4 exome AF: 6.84e-7 AC: 1AN: 1461676Hom.: 0 AF XY: 0.00000138 AC XY: 1AN XY: 727120
GnomAD4 genome Cov.: 32
ClinVar
Submissions by phenotype
not provided Pathogenic:1
The c.1123_1126delAACA pathogenic variant in the ALG11 gene has not been reported previously as a pathogenic variant nor as a benign variant, to our knowledge. This variant causes a frameshift starting with codon Asparagine 375, changes this amino acid to a Phenylalanine residue, and creates a premature Stop codon at position 6 of the new reading frame, denoted p.Asn375PheX6. This variant is predicted to cause loss of normal protein function either through protein truncation or nonsense-mediated mRNA decay. The c.1123_1126delAACA variant was not observed in approximately 6500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. We interpret c.1123_1126delAACA as a pathogenic variant. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at