2-55027029-T-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The ENST00000337526.11(RTN4):ā€‹c.1070A>Gā€‹(p.Asp357Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000103 in 1,461,282 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. D357V) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 32)
Exomes š‘“: 0.000010 ( 0 hom. )

Consequence

RTN4
ENST00000337526.11 missense

Scores

19

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.43
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]

Genome browser will be placed here

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=0.0747329).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
RTN4NM_020532.5 linkuse as main transcriptc.1070A>G p.Asp357Gly missense_variant 3/9 ENST00000337526.11 NP_065393.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
RTN4ENST00000337526.11 linkuse as main transcriptc.1070A>G p.Asp357Gly missense_variant 3/91 NM_020532.5 ENSP00000337838 Q9NQC3-1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD3 exomes
AF:
0.0000359
AC:
9
AN:
250684
Hom.:
0
AF XY:
0.0000369
AC XY:
5
AN XY:
135510
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000794
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000103
AC:
15
AN:
1461282
Hom.:
0
Cov.:
34
AF XY:
0.0000124
AC XY:
9
AN XY:
726962
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000126
Gnomad4 OTH exome
AF:
0.0000166
GnomAD4 genome
Cov.:
32
ExAC
AF:
0.0000659
AC:
8
EpiCase
AF:
0.00
EpiControl
AF:
0.000119

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.075
BayesDel_addAF
Benign
-0.31
T
BayesDel_noAF
Benign
-0.49
CADD
Benign
16
DANN
Benign
0.97
DEOGEN2
Benign
0.12
.;.;T;.;.
Eigen
Benign
-0.27
Eigen_PC
Benign
-0.36
FATHMM_MKL
Benign
0.38
N
LIST_S2
Benign
0.42
.;.;T;.;T
M_CAP
Benign
0.021
T
MetaRNN
Benign
0.075
T;T;T;T;T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
2.0
.;.;M;.;.
MutationTaster
Benign
1.0
D;D;D;N;N;N;N;N;N
PrimateAI
Benign
0.29
T
PROVEAN
Benign
-1.6
N;N;N;N;N
REVEL
Benign
0.14
Sift
Benign
0.13
T;T;D;T;T
Sift4G
Benign
0.15
T;T;T;T;T
Polyphen
0.95
.;.;P;.;.
Vest4
0.13
MutPred
0.13
.;.;Loss of solvent accessibility (P = 0.0477);.;.;
MVP
0.27
MPC
0.035
ClinPred
0.11
T
GERP RS
3.9
Varity_R
0.14
gMVP
0.064

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: rs11677099; hg19: chr2-55254165; API