rs4134932
Variant summary
Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BS1BS2
The NM_004722.4(AP4M1):c.1305C>T(p.Asn435=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0286 in 1,613,992 control chromosomes in the GnomAD database, including 834 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).
Frequency
Genomes: 𝑓 0.018 ( 44 hom., cov: 32)
Exomes 𝑓: 0.030 ( 790 hom. )
Consequence
AP4M1
NM_004722.4 synonymous
NM_004722.4 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 1.27
Genes affected
AP4M1 (HGNC:574): (adaptor related protein complex 4 subunit mu 1) This gene encodes a subunit of the heterotetrameric AP-4 complex. The encoded protein belongs to the adaptor complexes medium subunits family. This AP-4 complex is involved in the recognition and sorting of cargo proteins with tyrosine-based motifs from the trans-golgi network to the endosomal-lysosomal system. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -19 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.38).
BP6
?
Variant 7-100106825-C-T is Benign according to our data. Variant chr7-100106825-C-T is described in ClinVar as [Benign]. Clinvar id is 128404.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr7-100106825-C-T is described in Lovd as [Benign].
BP7
?
Synonymous conserved (PhyloP=1.27 with no splicing effect.
BS1
?
Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0184 (2800/152344) while in subpopulation NFE AF= 0.0299 (2031/68030). AF 95% confidence interval is 0.0288. There are 44 homozygotes in gnomad4. There are 1333 alleles in male gnomad4 subpopulation. This position pass quality control queck.
BS2
?
High Homozygotes in GnomAd at 44 AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
AP4M1 | NM_004722.4 | c.1305C>T | p.Asn435= | synonymous_variant | 15/15 | ENST00000359593.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
AP4M1 | ENST00000359593.9 | c.1305C>T | p.Asn435= | synonymous_variant | 15/15 | 1 | NM_004722.4 | P3 |
Frequencies
GnomAD3 genomes ? AF: 0.0184 AC: 2802AN: 152226Hom.: 44 Cov.: 32
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GnomAD3 exomes AF: 0.0191 AC: 4794AN: 251092Hom.: 77 AF XY: 0.0204 AC XY: 2776AN XY: 135830
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GnomAD4 exome AF: 0.0296 AC: 43296AN: 1461648Hom.: 790 Cov.: 34 AF XY: 0.0296 AC XY: 21519AN XY: 727142
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ClinVar
Significance: Benign
Submissions summary: Benign:4
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:2
Benign, criteria provided, single submitter | clinical testing | Genetic Services Laboratory, University of Chicago | Apr 01, 2013 | - - |
Benign, criteria provided, single submitter | clinical testing | GeneDx | Mar 01, 2016 | This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. - |
Hereditary spastic paraplegia Benign:1
Benign, criteria provided, single submitter | clinical testing | Genome Diagnostics Laboratory, The Hospital for Sick Children | Nov 27, 2021 | - - |
Hereditary spastic paraplegia 50 Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 29, 2024 | - - |
Computational scores
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BayesDel_noAF
Benign
Cadd
Benign
Dann
Benign
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at