chr2-54982573-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The ENST00000337526.11(RTN4):​c.3302G>A​(p.Cys1101Tyr) 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. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 31)

Consequence

RTN4
ENST00000337526.11 missense

Scores

5
14

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.37
Variant links:
Genes affected
RTN4 (HGNC:14085): (reticulon 4) This gene belongs to the family of reticulon encoding genes. Reticulons are associated with the endoplasmic reticulum, and are involved in neuroendocrine secretion or in membrane trafficking in neuroendocrine cells. The product of this gene is a potent neurite outgrowth inhibitor which may also help block the regeneration of the central nervous system in higher vertebrates. Alternatively spliced transcript variants derived both from differential splicing and differential promoter usage and encoding different isoforms have been identified. [provided by RefSeq, Jul 2008]

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.35641545).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
RTN4NM_020532.5 linkuse as main transcriptc.3302G>A p.Cys1101Tyr missense_variant 5/9 ENST00000337526.11 NP_065393.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
RTN4ENST00000337526.11 linkuse as main transcriptc.3302G>A p.Cys1101Tyr missense_variant 5/91 NM_020532.5 ENSP00000337838 Q9NQC3-1

Frequencies

GnomAD3 genomes
Cov.:
31
GnomAD4 exome
Cov.:
30
GnomAD4 genome
Cov.:
31
Alfa
AF:
0.0000936
Hom.:
0
Bravo
AF:
0.00000756

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingAmbry GeneticsApr 17, 2023The c.3302G>A (p.C1101Y) alteration is located in exon 5 (coding exon 5) of the RTN4 gene. This alteration results from a G to A substitution at nucleotide position 3302, causing the cysteine (C) at amino acid position 1101 to be replaced by a tyrosine (Y). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.18
BayesDel_addAF
Benign
-0.067
T
BayesDel_noAF
Benign
-0.33
CADD
Uncertain
24
DANN
Benign
0.89
DEOGEN2
Benign
0.31
.;.;.;T;.;.;.;.;.;.
Eigen
Uncertain
0.33
Eigen_PC
Uncertain
0.42
FATHMM_MKL
Uncertain
0.91
D
LIST_S2
Benign
0.58
T;.;.;T;T;T;.;T;T;T
M_CAP
Benign
0.0075
T
MetaRNN
Benign
0.36
T;T;T;T;T;T;T;T;T;T
MetaSVM
Benign
-0.67
T
MutationAssessor
Benign
1.6
.;.;.;L;.;.;.;.;.;.
MutationTaster
Benign
0.60
D;D;D;D;D;D;D;D;N;N
PrimateAI
Uncertain
0.52
T
PROVEAN
Uncertain
-4.1
D;D;D;D;D;D;D;D;.;D
REVEL
Benign
0.15
Sift
Benign
0.92
T;T;T;T;T;T;T;T;.;T
Sift4G
Benign
1.0
T;T;T;T;T;T;T;T;T;.
Polyphen
1.0, 0.020
.;.;.;D;.;B;.;.;.;.
Vest4
0.38
MutPred
0.55
.;.;.;Gain of catalytic residue at L1096 (P = 0.0636);.;.;.;.;.;.;
MVP
0.64
MPC
0.063
ClinPred
0.89
D
GERP RS
5.0
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
Varity_R
0.21
gMVP
0.64

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.0
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs1678227713; hg19: chr2-55209709; API