19-6309834-C-A
Variant summary
Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2PP3_Strong
The NM_133492.3(ACER1):c.351G>T(p.Arg117Ser) variant causes a missense, splice region change. The variant allele was found at a frequency of 0.00000744 in 1,613,754 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. 2/3 splice prediction tools predicting alterations to normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Consequence
NM_133492.3 missense, splice_region
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_pathogenic. Variant got 6 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
ACER1 | NM_133492.3 | c.351G>T | p.Arg117Ser | missense_variant, splice_region_variant | Exon 4 of 6 | ENST00000301452.5 | NP_597999.1 | |
ACER1 | XM_011527673.3 | c.222G>T | p.Arg74Ser | missense_variant, splice_region_variant | Exon 5 of 7 | XP_011525975.1 |
Ensembl
Frequencies
GnomAD3 genomes AF: 0.00000658 AC: 1AN: 152062Hom.: 0 Cov.: 31
GnomAD4 exome AF: 0.00000753 AC: 11AN: 1461692Hom.: 0 Cov.: 31 AF XY: 0.00000688 AC XY: 5AN XY: 727138
GnomAD4 genome AF: 0.00000658 AC: 1AN: 152062Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0AN XY: 74266
ClinVar
Submissions by phenotype
not specified Uncertain:1
The c.351G>T (p.R117S) alteration is located in exon 4 (coding exon 4) of the ACER1 gene. This alteration results from a G to T substitution at nucleotide position 351, causing the arginine (R) at amino acid position 117 to be replaced by a serine (S). 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