12-102958378-C-T
Variant summary
Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2
The NM_004316.4(ASCL1):c.134C>T(p.Ala45Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000142 in 1,478,948 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Consequence
NM_004316.4 missense
Scores
Clinical Significance
Conservation
Genome browser will be placed here
ACMG classification
Verdict is Benign. Variant got -8 ACMG points.
Transcripts
RefSeq
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
ASCL1 | ENST00000266744.4 | c.134C>T | p.Ala45Val | missense_variant | Exon 1 of 2 | 1 | NM_004316.4 | ENSP00000266744.3 | ||
PAH | ENST00000547319.1 | n.33G>A | non_coding_transcript_exon_variant | Exon 1 of 3 | 4 | |||||
PAH | ENST00000551337.5 | c.-279G>A | upstream_gene_variant | 3 | ENSP00000447620.1 | |||||
PAH | ENST00000635500.1 | n.-156G>A | upstream_gene_variant | 3 |
Frequencies
GnomAD3 genomes AF: 0.0000467 AC: 7AN: 149798Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.000134 AC: 11AN: 81802Hom.: 0 AF XY: 0.000107 AC XY: 5AN XY: 46806
GnomAD4 exome AF: 0.0000105 AC: 14AN: 1329044Hom.: 0 Cov.: 29 AF XY: 0.0000107 AC XY: 7AN XY: 655318
GnomAD4 genome AF: 0.0000467 AC: 7AN: 149904Hom.: 0 Cov.: 32 AF XY: 0.0000410 AC XY: 3AN XY: 73254
ClinVar
Submissions by phenotype
not specified Uncertain:1
The c.134C>T (p.A45V) alteration is located in exon 1 (coding exon 1) of the ASCL1 gene. This alteration results from a C to T substitution at nucleotide position 134, causing the alanine (A) at amino acid position 45 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at