12-102958393-CGCAGCAGCAGCAGCAGCAGCAGCAGCA-CGCAGCAGCAGCAGCAGCAGCAGCAGCAGCAGCAGCAGCAGCA
Variant summary
Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2
The NM_004316.4(ASCL1):c.172_186dupCAGCAGCAGCAGCAG(p.Gln58_Gln62dup) variant causes a conservative inframe insertion change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Uncertain significance (★★).
Frequency
Consequence
NM_004316.4 conservative_inframe_insertion
Scores
Clinical Significance
Conservation
Genome browser will be placed here
ACMG classification
Verdict is Likely_benign. Variant got -4 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
ASCL1 | NM_004316.4 | c.172_186dupCAGCAGCAGCAGCAG | p.Gln58_Gln62dup | conservative_inframe_insertion | Exon 1 of 2 | ENST00000266744.4 | NP_004307.2 | |
PAH | NM_001354304.2 | c.-309_-295dupTGCTGCTGCTGCTGC | 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_186dupCAGCAGCAGCAGCAG | p.Gln58_Gln62dup | conservative_inframe_insertion | Exon 1 of 2 | 1 | NM_004316.4 | ENSP00000266744.3 | ||
PAH | ENST00000547319.1 | n.3_17dupTGCTGCTGCTGCTGC | non_coding_transcript_exon_variant | Exon 1 of 3 | 4 | |||||
PAH | ENST00000551337.5 | c.-309_-295dupTGCTGCTGCTGCTGC | upstream_gene_variant | 3 | ENSP00000447620.1 |
Frequencies
GnomAD3 genomes AF: 0.00101 AC: 151AN: 150120Hom.: 0 Cov.: 0
GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.000702 AC: 952AN: 1356658Hom.: 1 Cov.: 17 AF XY: 0.000747 AC XY: 500AN XY: 669094
GnomAD4 genome AF: 0.00101 AC: 151AN: 150210Hom.: 0 Cov.: 0 AF XY: 0.00102 AC XY: 75AN XY: 73326
ClinVar
Submissions by phenotype
not specified Uncertain:1
The Gln51[17] variant in ASCL1 (alternate gene names: MASH1 or HASH1) represents one of several alleles of a poly-glutamine tract of variable length. The Gln51[ 12] allele represents the reference sequence (hg19). This variant has been ident ified by our laboratory in one Caucasian individual with pulmonary fibrosis (LMM unpublished data). In addition, this variant has also been reported in 0.1% (1/ 1604) of Japanese control chromosomes (Ide 2005) and in 0.3% (1/304) of Caucasia n control chromosomes tested by our laboratory. Computational prediction tools a nd conservation analysis are limited or unavailable for this variant. In summary , the clinical significance of the Gln51[17] variant is uncertain. -
not provided Uncertain:1
- -
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