chr10-104915823-T-G
Variant summary
Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2
The NM_014978.3(SORCS3):c.696-10T>G variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000829 in 1,613,344 control chromosomes in the GnomAD database, including 13 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).
Frequency
Genomes: 𝑓 0.0037 ( 5 hom., cov: 32)
Exomes 𝑓: 0.00053 ( 8 hom. )
Consequence
SORCS3
NM_014978.3 splice_polypyrimidine_tract, intron
NM_014978.3 splice_polypyrimidine_tract, intron
Scores
2
Splicing: ADA: 0.001994
2
Clinical Significance
Conservation
PhyloP100: 0.116
Genes affected
SORCS3 (HGNC:16699): (sortilin related VPS10 domain containing receptor 3) This gene encodes a type-I receptor transmembrane protein that is a member of the vacuolar protein sorting 10 receptor family. Proteins of this family are defined by a vacuolar protein sorting 10 domain at the N-terminus. The N-terminal segment of this domain has a consensus motif for proprotein convertase processing, and the C-terminal segment of this domain is characterized by ten conserved cysteine residues. The vacuolar protein sorting 10 domain is followed by a leucine-rich segment, a transmembrane domain, and a short C-terminal cytoplasmic domain that interacts with adaptor molecules. The transcript is expressed at high levels in the brain, and candidate gene studies suggest that genetic variation in this gene is associated with Alzheimer's disease. Consistent with this observation, knockdown of the gene in cell culture results in an increase in amyloid precursor protein processing. [provided by RefSeq, Dec 2014]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -10 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.64).
BP6
?
Variant 10-104915823-T-G is Benign according to our data. Variant chr10-104915823-T-G is described in ClinVar as [Benign]. Clinvar id is 768388.Status of the report is criteria_provided_single_submitter, 1 stars.
BS2
?
High Homozygotes in GnomAd at 5 gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SORCS3 | NM_014978.3 | c.696-10T>G | splice_polypyrimidine_tract_variant, intron_variant | ENST00000369701.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SORCS3 | ENST00000369701.8 | c.696-10T>G | splice_polypyrimidine_tract_variant, intron_variant | 1 | NM_014978.3 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.00371 AC: 565AN: 152164Hom.: 5 Cov.: 32
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GnomAD3 exomes AF: 0.00135 AC: 340AN: 251134Hom.: 4 AF XY: 0.000869 AC XY: 118AN XY: 135748
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GnomAD4 exome AF: 0.000527 AC: 770AN: 1461062Hom.: 8 Cov.: 29 AF XY: 0.000443 AC XY: 322AN XY: 726894
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ClinVar
Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Dec 20, 2018 | - - |
Computational scores
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Name
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BayesDel_noAF
Benign
Cadd
Benign
Dann
Benign
Splicing
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dbscSNV1_ADA
Benign
dbscSNV1_RF
Benign
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at