rs371976817
Variant summary
Our verdict is Benign. Variant got -10 ACMG points: 2P and 12B. PP3_ModerateBP6_Very_StrongBS2
The NM_018026.4(PACS1):c.2776+5G>A variant causes a splice donor 5th base, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000936 in 1,613,740 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 2/3 splice prediction tools predicting alterations to normal splicing. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Consequence
NM_018026.4 splice_donor_5th_base, intron
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -10 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
PACS1 | NM_018026.4 | c.2776+5G>A | splice_donor_5th_base_variant, intron_variant | ENST00000320580.9 | NP_060496.2 | |||
PACS1 | XM_011545162.2 | c.2482+5G>A | splice_donor_5th_base_variant, intron_variant | XP_011543464.2 | ||||
PACS1 | XM_011545164.3 | c.2437+5G>A | splice_donor_5th_base_variant, intron_variant | XP_011543466.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
PACS1 | ENST00000320580.9 | c.2776+5G>A | splice_donor_5th_base_variant, intron_variant | 1 | NM_018026.4 | ENSP00000316454 | P2 |
Frequencies
GnomAD3 genomes AF: 0.0000132 AC: 2AN: 152028Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000239 AC: 6AN: 251202Hom.: 0 AF XY: 0.0000295 AC XY: 4AN XY: 135760
GnomAD4 exome AF: 0.000102 AC: 149AN: 1461712Hom.: 0 Cov.: 32 AF XY: 0.0000990 AC XY: 72AN XY: 727182
GnomAD4 genome AF: 0.0000132 AC: 2AN: 152028Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 74246
ClinVar
Submissions by phenotype
not specified Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Genetic Services Laboratory, University of Chicago | Mar 04, 2015 | - - |
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Oct 21, 2020 | In silico analysis, which includes splice predictors and evolutionary conservation, supports a deleterious effect; Has not been previously published as pathogenic or benign to our knowledge - |
Schuurs-Hoeijmakers syndrome Benign:1
Benign, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Jan 22, 2024 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at