rs372511561
Variant summary
Our verdict is Likely benign. Variant got -3 ACMG points: 2P and 5B. PM2BP4_StrongBP6
The NM_004722.4(AP4M1):c.544-6T>G variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000586 in 1,613,798 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 2/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Consequence
NM_004722.4 splice_region, splice_polypyrimidine_tract, intron
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -3 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
AP4M1 | NM_004722.4 | c.544-6T>G | splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant | ENST00000359593.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
AP4M1 | ENST00000359593.9 | c.544-6T>G | splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant | 1 | NM_004722.4 | P3 |
Frequencies
GnomAD3 genomes ? AF: 0.000434 AC: 66AN: 152044Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.000326 AC: 82AN: 251330Hom.: 0 AF XY: 0.000302 AC XY: 41AN XY: 135880
GnomAD4 exome AF: 0.000601 AC: 879AN: 1461636Hom.: 1 Cov.: 31 AF XY: 0.000542 AC XY: 394AN XY: 727130
GnomAD4 genome ? AF: 0.000434 AC: 66AN: 152162Hom.: 0 Cov.: 32 AF XY: 0.000336 AC XY: 25AN XY: 74396
ClinVar
Submissions by phenotype
not provided Uncertain:1Benign:1
Likely benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Jul 01, 2024 | AP4M1: BP4 - |
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | May 15, 2023 | Has not been previously published as pathogenic or benign to our knowledge; In silico analysis suggests this variant may impact gene splicing. In the absence of RNA/functional studies, the actual effect of this sequence change is unknown. - |
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Genetic Services Laboratory, University of Chicago | Aug 26, 2016 | - - |
Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | May 29, 2024 | The c.544-6T>G intronic alteration consists of a T to G substitution 6 nucleotides before exon 7 of the AP4M1 gene. Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Hereditary spastic paraplegia 50 Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Jan 18, 2024 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at