rs751412092
Variant names:
Variant summary
Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2
The NM_003105.6(SORL1):c.76G>C(p.Ala26Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).
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
6
10
Clinical Significance
Conservation
PhyloP100: 1.77
Publications
0 publications found
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 was made for transcript
Our verdict: Uncertain_significance. The variant received 2 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
Variant Effect in Transcripts
ACMG analysis was done for transcript: NM_003105.6. You can select a different transcript below to see updated ACMG assignments.
Ensembl Transcripts
| Sel. | Gene | Transcript | Tags | HGVSc | HGVSp | Effect | Exon Rank | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|---|
| SORL1 | TSL:1 MANE Select | c.76G>C | p.Ala26Pro | missense | Exon 1 of 48 | ENSP00000260197.6 | Q92673 | ||
| SORL1 | TSL:1 | n.28G>C | non_coding_transcript_exon | Exon 1 of 15 | |||||
| SORL1-AS1 | TSL:2 MANE Select | n.293+268C>G | intron | N/A |
Frequencies
GnomAD3 genomes
GnomAD3 genomes
Cov.:
32
GnomAD2 exomes AF: 0.00 AC: 0AN: 124494 AF XY: 0.00
GnomAD2 exomes
AF:
AC:
0
AN:
124494
AF XY:
Gnomad AFR exome
AF:
Gnomad AMR exome
AF:
Gnomad ASJ exome
AF:
Gnomad EAS exome
AF:
Gnomad FIN exome
AF:
Gnomad NFE exome
AF:
Gnomad OTH exome
AF:
GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0AN: 1376498Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0AN XY: 679720
GnomAD4 exome
Data not reliable, filtered out with message: AC0
AF:
AC:
0
AN:
1376498
Hom.:
Cov.:
31
AF XY:
AC XY:
0
AN XY:
679720
African (AFR)
AF:
AC:
0
AN:
28000
American (AMR)
AF:
AC:
0
AN:
33738
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
24080
East Asian (EAS)
AF:
AC:
0
AN:
31836
South Asian (SAS)
AF:
AC:
0
AN:
76638
European-Finnish (FIN)
AF:
AC:
0
AN:
47918
Middle Eastern (MID)
AF:
AC:
0
AN:
4136
European-Non Finnish (NFE)
AF:
AC:
0
AN:
1073276
Other (OTH)
AF:
AC:
0
AN:
56876
GnomAD4 genome
GnomAD4 genome
Cov.:
32
ExAC
AF:
AC:
1
ClinVar
ClinVar submissions
View on ClinVar Significance:Uncertain significance
Revision:criteria provided, single submitter
Pathogenic
VUS
Benign
Condition
-
1
-
not provided (1)
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Uncertain
D
BayesDel_noAF
Benign
DANN
Uncertain
DEOGEN2
Benign
T
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Benign
N
LIST_S2
Benign
T
M_CAP
Pathogenic
D
MetaRNN
Uncertain
T
MetaSVM
Uncertain
D
MutationAssessor
Benign
L
PhyloP100
PrimateAI
Pathogenic
D
PROVEAN
Benign
N
REVEL
Uncertain
Sift
Uncertain
D
Sift4G
Benign
T
Polyphen
P
Vest4
MutPred
Gain of glycosylation at A26 (P = 0.0736)
MVP
MPC
ClinPred
D
GERP RS
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
Publications
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