12-102958393-CGCAGCAGCAGCAGCAGCAGCAGCAGCA-CGCAGCAGCAGCA
Variant summary
Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP6_ModerateBS2
The NM_004316.4(ASCL1):c.172_186delCAGCAGCAGCAGCAG(p.Gln58_Gln62del) variant causes a conservative inframe deletion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0042 in 1,507,022 control chromosomes in the GnomAD database, including 10 homozygotes. Variant has been reported in ClinVar as Likely benign (★).
Frequency
Consequence
NM_004316.4 conservative_inframe_deletion
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -6 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
ASCL1 | NM_004316.4 | c.172_186delCAGCAGCAGCAGCAG | p.Gln58_Gln62del | conservative_inframe_deletion | Exon 1 of 2 | ENST00000266744.4 | NP_004307.2 | |
PAH | NM_001354304.2 | c.-309_-295delTGCTGCTGCTGCTGC | 5_prime_UTR_variant | Exon 1 of 14 | NP_001341233.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
ASCL1 | ENST00000266744.4 | c.172_186delCAGCAGCAGCAGCAG | p.Gln58_Gln62del | conservative_inframe_deletion | Exon 1 of 2 | 1 | NM_004316.4 | ENSP00000266744.3 | ||
PAH | ENST00000547319.1 | n.3_17delTGCTGCTGCTGCTGC | non_coding_transcript_exon_variant | Exon 1 of 3 | 4 | |||||
PAH | ENST00000551337.5 | c.-309_-295delTGCTGCTGCTGCTGC | upstream_gene_variant | 3 | ENSP00000447620.1 |
Frequencies
GnomAD3 genomes AF: 0.00291 AC: 437AN: 150120Hom.: 1 Cov.: 0
GnomAD4 exome AF: 0.00435 AC: 5896AN: 1356812Hom.: 9 AF XY: 0.00423 AC XY: 2831AN XY: 669150
GnomAD4 genome AF: 0.00291 AC: 437AN: 150210Hom.: 1 Cov.: 0 AF XY: 0.00288 AC XY: 211AN XY: 73326
ClinVar
Submissions by phenotype
not provided Benign:3
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The ASCL1 p.Gln58_Gln62del variant was not identified in the literature but was identified in dbSNP (ID: rs3832799), ClinVar (classified as likely benign by PreventionGenetics and EGL Genetic Diagnostics), and LOVD 3.0 (classified as likely benign by VKGL-NL_Rotterdam and VKGL-NL_Groningen). The variant was not identified in the following control databases: the 1000 Genomes Project, the NHLBI GO Exome Sequencing Project, or the Genome Aggregation Database (March 6, 2019, v2.1.1). This variant is an in-frame deletion resulting in the removal of a string of glutamine (gln) residues from codons 58-62; this deletion is found within a glutamine repeat region and is not expected to have a functional impact. The variant occurs outside of the splicing consensus sequence and in silico or computational prediction software programs (SpliceSiteFinder, MaxEntScan, NNSPLICE, GeneSplicer) do not predict a difference in splicing. In summary, based on the above information the clinical significance of this variant cannot be determined with certainty at this time although we would lean towards a more benign role for this variant. This variant is classified as likely benign. -
not specified Benign:1
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ASCL1-related disorder Benign:1
This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at