17-1936748-G-T

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BP4_Strong

The NM_178568.4(RTN4RL1):​c.1074C>A​(p.Asn358Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000438 in 1,597,100 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000026 ( 0 hom., cov: 33)
Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

RTN4RL1
NM_178568.4 missense

Scores

1
18

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.20
Variant links:
Genes affected
RTN4RL1 (HGNC:21329): (reticulon 4 receptor like 1) Enables signaling receptor activity. Predicted to be involved in negative regulation of axon regeneration. 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 Likely_benign. Variant got -4 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.06669623).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
RTN4RL1NM_178568.4 linkc.1074C>A p.Asn358Lys missense_variant 2/2 ENST00000331238.7 NP_848663.1 Q86UN2

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
RTN4RL1ENST00000331238.7 linkc.1074C>A p.Asn358Lys missense_variant 2/21 NM_178568.4 ENSP00000330631.4 Q86UN2

Frequencies

GnomAD3 genomes
AF:
0.0000263
AC:
4
AN:
152234
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000196
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:
0.000478
GnomAD3 exomes
AF:
0.00000878
AC:
2
AN:
227838
Hom.:
0
AF XY:
0.0000161
AC XY:
2
AN XY:
124200
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:
0.0000367
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00000970
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000208
AC:
3
AN:
1444866
Hom.:
0
Cov.:
71
AF XY:
0.00000279
AC XY:
2
AN XY:
718122
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:
0.0000240
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.0000168
GnomAD4 genome
AF:
0.0000263
AC:
4
AN:
152234
Hom.:
0
Cov.:
33
AF XY:
0.0000269
AC XY:
2
AN XY:
74372
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.000196
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:
0.000478
Bravo
AF:
0.000102

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 GeneticsSep 27, 2021The c.1074C>A (p.N358K) alteration is located in exon 2 (coding exon 2) of the RTN4RL1 gene. This alteration results from a C to A substitution at nucleotide position 1074, causing the asparagine (N) at amino acid position 358 to be replaced by a lysine (K). 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
0.23
BayesDel_addAF
Benign
-0.36
T
BayesDel_noAF
Benign
-0.65
CADD
Benign
15
DANN
Benign
0.94
DEOGEN2
Benign
0.037
T
Eigen
Benign
-0.32
Eigen_PC
Benign
-0.14
FATHMM_MKL
Uncertain
0.92
D
LIST_S2
Benign
0.62
T
M_CAP
Benign
0.014
T
MetaRNN
Benign
0.067
T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
0.69
N
PrimateAI
Benign
0.46
T
PROVEAN
Benign
-0.28
N
REVEL
Benign
0.067
Sift
Benign
1.0
T
Sift4G
Benign
0.97
T
Polyphen
0.0010
B
Vest4
0.12
MutPred
0.31
Gain of catalytic residue at N358 (P = 0.0049);
MVP
0.25
MPC
0.42
ClinPred
0.073
T
GERP RS
4.3
Varity_R
0.054
gMVP
0.13

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: rs1013199849; hg19: chr17-1840042; API