chrX-15827324-G-A
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Variant summary
Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2
The NM_001272071.2(AP1S2):c.*1C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000257 in 1,205,012 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 18 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.000027 ( 0 hom., 1 hem., cov: 22)
Exomes 𝑓: 0.000026 ( 0 hom. 17 hem. )
Consequence
AP1S2
NM_001272071.2 3_prime_UTR
NM_001272071.2 3_prime_UTR
Scores
2
Clinical Significance
Conservation
PhyloP100: 1.47
Genes affected
AP1S2 (HGNC:560): (adaptor related protein complex 1 subunit sigma 2) Adaptor protein complex 1 is found at the cytoplasmic face of coated vesicles located at the Golgi complex, where it mediates both the recruitment of clathrin to the membrane and the recognition of sorting signals within the cytosolic tails of transmembrane receptors. This complex is a heterotetramer composed of two large, one medium, and one small adaptin subunit. The protein encoded by this gene serves as the small subunit of this complex and is a member of the adaptin protein family. Transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jan 2013]
ZRSR2 (HGNC:23019): (zinc finger CCCH-type, RNA binding motif and serine/arginine rich 2) This gene encodes an essential splicing factor. The encoded protein associates with the U2 auxiliary factor heterodimer, which is required for the recognition of a functional 3' splice site in pre-mRNA splicing, and may play a role in network interactions during spliceosome assembly. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -6 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.3).
BS2
High Hemizygotes in GnomAdExome4 at 17 XL gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
AP1S2 | NM_001272071.2 | c.*1C>T | 3_prime_UTR_variant | 6/6 | ENST00000672987.1 | ||
AP1S2 | NM_003916.5 | c.*1C>T | 3_prime_UTR_variant | 5/5 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
AP1S2 | ENST00000672987.1 | c.*1C>T | 3_prime_UTR_variant | 6/6 | NM_001272071.2 | P3 |
Frequencies
GnomAD3 genomes AF: 0.0000268 AC: 3AN: 112121Hom.: 0 Cov.: 22 AF XY: 0.0000292 AC XY: 1AN XY: 34281
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GnomAD3 exomes AF: 0.0000382 AC: 7AN: 183221Hom.: 0 AF XY: 0.0000738 AC XY: 5AN XY: 67717
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GnomAD4 exome AF: 0.0000256 AC: 28AN: 1092891Hom.: 0 Cov.: 28 AF XY: 0.0000473 AC XY: 17AN XY: 359087
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GnomAD4 genome AF: 0.0000268 AC: 3AN: 112121Hom.: 0 Cov.: 22 AF XY: 0.0000292 AC XY: 1AN XY: 34281
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Jan 26, 2017 | The c.*1C>T variant is located in the 3' untranslated region (3’ UTR) of the AP1S2 gene. This variant results from a C to T substitution one nucleotide after the last translated codon. This nucleotide position is not well conserved in available vertebrate species. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. - |
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