rs794727999
Variant summary
Our verdict is Uncertain significance. Variant got 5 ACMG points: 5P and 0B. PM2PP2PP3PP5
The NM_005045.4(RELN):c.9526G>A(p.Glu3176Lys) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Pathogenic (no stars). Synonymous variant affecting the same amino acid position (i.e. E3176E) has been classified as Likely benign.
Frequency
Genomes: not found (cov: 32)
Consequence
RELN
NM_005045.4 missense
NM_005045.4 missense
Scores
4
6
9
Clinical Significance
Conservation
PhyloP100: 7.36
Genes affected
RELN (HGNC:9957): (reelin) This gene encodes a large secreted extracellular matrix protein thought to control cell-cell interactions critical for cell positioning and neuronal migration during brain development. This protein may be involved in schizophrenia, autism, bipolar disorder, major depression and in migration defects associated with temporal lobe epilepsy. Mutations of this gene are associated with autosomal recessive lissencephaly with cerebellar hypoplasia. Two transcript variants encoding distinct isoforms have been identified for this gene. Other transcript variants have been described but their full length nature has not been determined. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 5 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
PP2
?
Missense variant where missense usually causes diseases, RELN
PP3
?
MetaRNN computational evidence supports a deleterious effect, 0.804
PP5
?
Variant 7-103490747-C-T is Pathogenic according to our data. Variant chr7-103490747-C-T is described in ClinVar as [Pathogenic]. Clinvar id is 199435.Status of the report is no_assertion_criteria_provided, 0 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
RELN | NM_005045.4 | c.9526G>A | p.Glu3176Lys | missense_variant | 59/65 | ENST00000428762.6 | |
SLC26A5-AS1 | NR_110141.1 | n.1366-13657C>T | intron_variant, non_coding_transcript_variant | ||||
RELN | NM_173054.3 | c.9526G>A | p.Glu3176Lys | missense_variant | 59/64 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
RELN | ENST00000428762.6 | c.9526G>A | p.Glu3176Lys | missense_variant | 59/65 | 5 | NM_005045.4 | P5 | |
SLC26A5-AS1 | ENST00000422488.1 | n.1366-13657C>T | intron_variant, non_coding_transcript_variant | 1 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD3 genomes
?
Cov.:
32
GnomAD4 exome Cov.: 31
GnomAD4 exome
Cov.:
31
GnomAD4 genome ? Cov.: 32
GnomAD4 genome
?
Cov.:
32
ClinVar
Significance: Pathogenic
Submissions summary: Pathogenic:1Other:1
Revision: no assertion criteria provided
LINK: link
Submissions by phenotype
Familial temporal lobe epilepsy 7 Pathogenic:1Other:1
not provided, no classification provided | literature only | GeneReviews | - | - - |
Pathogenic, no assertion criteria provided | literature only | OMIM | Jun 04, 2015 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
Cadd
Pathogenic
Dann
Pathogenic
DEOGEN2
Benign
T;.;.
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Pathogenic
D
LIST_S2
Uncertain
D;D;D
M_CAP
Benign
T
MetaRNN
Pathogenic
D;D;D
MetaSVM
Benign
T
MutationAssessor
Uncertain
M;M;.
MutationTaster
Benign
D;D;D
PrimateAI
Pathogenic
D
PROVEAN
Benign
N;N;N
REVEL
Benign
Sift
Uncertain
D;D;D
Sift4G
Uncertain
D;D;D
Polyphen
P;D;.
Vest4
MutPred
Gain of methylation at E3176 (P = 0.0118);Gain of methylation at E3176 (P = 0.0118);Gain of methylation at E3176 (P = 0.0118);
MVP
MPC
ClinPred
D
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