12-102958393-CGCAGCAGCAGCAGCAGCAGCAGCAGCA-CGCAGCAGCAGCAGCAGCAGCAGCAGCAGCAGCAGCAGCA
Variant summary
Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP6BS1BS2
The NM_004316.4(ASCL1):c.175_186dupCAGCAGCAGCAG(p.Gln59_Gln62dup) variant causes a conservative inframe insertion change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Consequence
NM_004316.4 conservative_inframe_insertion
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -9 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
ASCL1 | NM_004316.4 | c.175_186dupCAGCAGCAGCAG | p.Gln59_Gln62dup | conservative_inframe_insertion | Exon 1 of 2 | ENST00000266744.4 | NP_004307.2 | |
PAH | NM_001354304.2 | c.-306_-295dupTGCTGCTGCTGC | 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.175_186dupCAGCAGCAGCAG | p.Gln59_Gln62dup | conservative_inframe_insertion | Exon 1 of 2 | 1 | NM_004316.4 | ENSP00000266744.3 | ||
PAH | ENST00000547319.1 | n.6_17dupTGCTGCTGCTGC | non_coding_transcript_exon_variant | Exon 1 of 3 | 4 | |||||
PAH | ENST00000551337.5 | c.-306_-295dupTGCTGCTGCTGC | upstream_gene_variant | 3 | ENSP00000447620.1 |
Frequencies
GnomAD3 genomes AF: 0.0157 AC: 2357AN: 150106Hom.: 35 Cov.: 0
GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00919 AC: 12466AN: 1356242Hom.: 12 Cov.: 17 AF XY: 0.00896 AC XY: 5996AN XY: 668922
GnomAD4 genome AF: 0.0157 AC: 2353AN: 150196Hom.: 35 Cov.: 0 AF XY: 0.0151 AC XY: 1104AN XY: 73316
ClinVar
Submissions by phenotype
not specified Uncertain:1Benign:3
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Variant classified as Uncertain Significance - Favor Benign. The Gln51[16] varia nt in ASCL1 (alternate gene names: MASH1 or HASH1) represents one of several all eles of a poly-glutamine tract of variable length. The Gln51[12] allele represen ts the reference sequence (hg19). This variant has not been previously reported in individuals with pulmonary disease, but has been reported in 0.7% (11/1604) o f Japanese control chromosomes (Ide 2005). Computational prediction tools and co nservation analysis are limited or unavailable for this variant. In summary, whi le the clinical significance of the Gln51[16] variant is uncertain, its frequenc y suggests that it is more likely to be benign. -
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