2-73572423-C-T
Variant summary
Our verdict is Pathogenic. Variant got 18 ACMG points: 18P and 0B. PVS1PM2PP5_Very_Strong
The NM_001378454.1(ALMS1):c.10546C>T(p.Gln3516*) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000132 in 151,740 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 Likely pathogenic (★★). Synonymous variant affecting the same amino acid position (i.e. Q3516Q) has been classified as Likely benign. Variant results in nonsense mediated mRNA decay.
Frequency
Consequence
NM_001378454.1 stop_gained
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Pathogenic. Variant got 18 ACMG points.
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes AF: 0.0000132 AC: 2AN: 151740Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.00000404 AC: 1AN: 247272Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 134016
GnomAD4 exome Cov.: 31
GnomAD4 genome AF: 0.0000132 AC: 2AN: 151740Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1AN XY: 74128
ClinVar
Submissions by phenotype
Alstrom syndrome Pathogenic:3
For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 551455). This premature translational stop signal has been observed in individual(s) with Alström syndrome (PMID: 17594715, 32531870). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Gln3517*) in the ALMS1 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in ALMS1 are known to be pathogenic (PMID: 17594715). -
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Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at