rs372705427
Variant names:
Your query was ambiguous. Multiple possible variants found:
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_003105.6(SORL1):c.227C>A(p.Pro76Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.
Frequency
Genomes: not found (cov: 32)
Exomes 𝑓: 0.0 ( 0 hom. )
Failed GnomAD Quality Control
Consequence
SORL1
NM_003105.6 missense
NM_003105.6 missense
Scores
2
17
Clinical Significance
Not reported in ClinVar
Conservation
PhyloP100: -0.241
Genes affected
SORL1 (HGNC:11185): (sortilin related receptor 1) This gene encodes a mosaic protein that belongs to at least two families: the vacuolar protein sorting 10 (VPS10) domain-containing receptor family, and the low density lipoprotein receptor (LDLR) family. The encoded protein also contains fibronectin type III repeats and an epidermal growth factor repeat. The encoded preproprotein is proteolytically processed to generate the mature receptor, which likely plays roles in endocytosis and sorting. Mutations in this gene may be associated with Alzheimer's disease. [provided by RefSeq, Feb 2016]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 0 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.104257405).
Transcripts
RefSeq
| Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|
| SORL1 | NM_003105.6 | c.227C>A | p.Pro76Gln | missense_variant | Exon 1 of 48 | ENST00000260197.12 | NP_003096.2 | |
| SORL1-AS1 | NR_183636.1 | n.293+117G>T | intron_variant | Intron 1 of 2 |
Ensembl
| Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
|---|---|---|---|---|---|---|---|---|---|---|
| SORL1 | ENST00000260197.12 | c.227C>A | p.Pro76Gln | missense_variant | Exon 1 of 48 | 1 | NM_003105.6 | ENSP00000260197.6 | ||
| SORL1 | ENST00000532451.1 | n.179C>A | non_coding_transcript_exon_variant | Exon 1 of 15 | 1 | |||||
| SORL1-AS1 | ENST00000501964.1 | n.339+117G>T | intron_variant | Intron 1 of 1 | 2 | |||||
| SORL1-AS1 | ENST00000529160.1 | n.245+117G>T | intron_variant | Intron 1 of 1 | 2 |
Frequencies
GnomAD3 genomes
GnomAD3 genomes
Cov.:
32
GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0AN: 1358984Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0AN XY: 671646
GnomAD4 exome
Data not reliable, filtered out with message: AC0
AF:
AC:
0
AN:
1358984
Hom.:
Cov.:
31
AF XY:
AC XY:
0
AN XY:
671646
Gnomad4 AFR exome
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GnomAD4 genome
GnomAD4 genome
Cov.:
32
ClinVar
Not reported inComputational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
DEOGEN2
Benign
T
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Benign
N
LIST_S2
Benign
T
M_CAP
Uncertain
D
MetaRNN
Benign
T
MetaSVM
Benign
T
MutationAssessor
Benign
L
PrimateAI
Uncertain
T
PROVEAN
Benign
N
REVEL
Benign
Sift
Benign
T
Sift4G
Benign
T
Polyphen
B
Vest4
MutPred
Loss of methylation at R71 (P = 0.0919);
MVP
MPC
ClinPred
T
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
Varity_R
gMVP
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at