11-57476739-C-T

Variant summary

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

The NM_178570.3(RTN4RL2):​c.1091C>T​(p.Ala364Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000345 in 1,447,682 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000020 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0000015 ( 0 hom. )

Consequence

RTN4RL2
NM_178570.3 missense

Scores

2
1
16

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.841
Variant links:
Genes affected
RTN4RL2 (HGNC:23053): (reticulon 4 receptor like 2) Enables signaling receptor activity. Predicted to be involved in cell surface receptor signaling pathway; corpus callosum development; and negative regulation of neuron projection development. Located in cell surface. Is anchored component of plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

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=0.16882786).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
RTN4RL2NM_178570.3 linkc.1091C>T p.Ala364Val missense_variant Exon 3 of 3 ENST00000335099.8 NP_848665.1 Q86UN3-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
RTN4RL2ENST00000335099.8 linkc.1091C>T p.Ala364Val missense_variant Exon 3 of 3 1 NM_178570.3 ENSP00000335397.3 Q86UN3-1
ENSG00000255301ENST00000528885.1 linkn.539-101G>A intron_variant Intron 1 of 1 2

Frequencies

GnomAD3 genomes
AF:
0.0000197
AC:
3
AN:
152092
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0000724
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.00
GnomAD4 exome
AF:
0.00000154
AC:
2
AN:
1295590
Hom.:
0
Cov.:
32
AF XY:
0.00000158
AC XY:
1
AN XY:
633992
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:
0.00000192
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.0000197
AC:
3
AN:
152092
Hom.:
0
Cov.:
32
AF XY:
0.0000135
AC XY:
1
AN XY:
74296
show subpopulations
Gnomad4 AFR
AF:
0.0000724
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.0000491

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Mar 01, 2025
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.1091C>T (p.A364V) alteration is located in exon 3 (coding exon 3) of the RTN4RL2 gene. This alteration results from a C to T substitution at nucleotide position 1091, causing the alanine (A) at amino acid position 364 to be replaced by a valine (V). 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
0.086
BayesDel_addAF
Benign
-0.15
T
BayesDel_noAF
Benign
-0.45
CADD
Benign
22
DANN
Uncertain
1.0
DEOGEN2
Benign
0.085
T
Eigen
Benign
-0.29
Eigen_PC
Benign
-0.29
FATHMM_MKL
Benign
0.15
N
LIST_S2
Benign
0.71
T
M_CAP
Pathogenic
0.55
D
MetaRNN
Benign
0.17
T
MetaSVM
Benign
-1.1
T
MutationAssessor
Benign
0.55
N
PrimateAI
Pathogenic
0.89
D
PROVEAN
Benign
-0.87
N
REVEL
Benign
0.10
Sift
Benign
0.38
T
Sift4G
Benign
0.33
T
Polyphen
0.96
D
Vest4
0.083
MutPred
0.18
Loss of loop (P = 0.0512);
MVP
0.67
MPC
1.4
ClinPred
0.25
T
GERP RS
2.4
Varity_R
0.16
gMVP
0.30

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: rs1022208001; hg19: chr11-57244212; API