Variant 22-20242067-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_023004.6(RTN4R):c.1066G>A(p.Gly356Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000192 in 1,612,534 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 0.00010 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000010 ( 0 hom. )

Consequence

RTN4R
NM_023004.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.312

Variant links:

Genes affected

RTN4R (HGNC:18601): (reticulon 4 receptor) This gene encodes the receptor for reticulon 4, oligodendrocyte myelin glycoprotein and myelin-associated glycoprotein. This receptor mediates axonal growth inhibition and may play a role in regulating axonal regeneration and plasticity in the adult central nervous system. [provided by RefSeq, Jul 2008]

RTN4R links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.08733457).

BS2

High AC in GnomAd at 16 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RTN4R	NM_023004.6 linkuse as main transcript	c.1066G>A	p.Gly356Ser	missense_variant	2/2	ENST00000043402.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
RTN4R	ENST00000043402.8 linkuse as main transcript	c.1066G>A	p.Gly356Ser	missense_variant	2/2	1	NM_023004.6	P1
RTN4R	ENST00000425986.1 linkuse as main transcript	c.1324G>A	p.Gly442Ser	missense_variant	2/2	2
RTN4R	ENST00000416372.5 linkuse as main transcript	c.1126G>A	p.Gly376Ser	missense_variant	2/2	3

Frequencies

GnomAD3 genomes

AF:

0.000105

AC:

AN:

152280

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000362

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:

0.000478

GnomAD3 exomes

AF:

0.0000363

AC:

AN:

247850

Hom.:

AF XY:

0.0000371

AC XY:

AN XY:

134890

show subpopulations

Gnomad AFR exome

AF:

0.000319

Gnomad AMR exome

AF:

0.000116

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:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000103

AC:

AN:

1460136

Hom.:

Cov.:

AF XY:

0.00000964

AC XY:

AN XY:

726376

show subpopulations

Gnomad4 AFR exome

AF:

0.000299

Gnomad4 AMR exome

AF:

0.0000671

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:

0.00

Gnomad4 OTH exome

AF:

0.0000331

GnomAD4 genome

AF:

0.000105

AC:

AN:

152398

Hom.:

Cov.:

AF XY:

0.0000537

AC XY:

AN XY:

74526

show subpopulations

Gnomad4 AFR

AF:

0.000361

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:

0.000473

Alfa

AF:

0.0000712

Hom.:

Bravo

AF:

0.000144

ESP6500AA

AF:

0.000455

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.0000495

AC:

EpiCase

AF:

0.00

EpiControl

AF:

0.0000593

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 submitter

clinical testing

Ambry Genetics

Apr 27, 2022

The c.1066G>A (p.G356S) alteration is located in exon 2 (coding exon 2) of the RTN4R gene. This alteration results from a G to A substitution at nucleotide position 1066, causing the glycine (G) at amino acid position 356 to be replaced by a serine (S). 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

0.10

BayesDel_addAF

Benign

-0.27

BayesDel_noAF

Benign

-0.34

Cadd

Benign

Dann

Uncertain

0.99

DEOGEN2

Benign

0.15

Eigen

Benign

-0.26

Eigen_PC

Benign

-0.30

FATHMM_MKL

Benign

0.59

LIST_S2

Benign

0.82

M_CAP

Uncertain

0.13

MetaRNN

Benign

0.087

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.9

MutationTaster

Benign

0.85

PrimateAI

Uncertain

0.78

PROVEAN

Benign

-0.79

REVEL

Benign

0.14

Sift

Benign

0.30

Sift4G

Benign

0.58

Polyphen

0.96

Vest4

0.099

MVP

0.73

MPC

0.45

ClinPred

0.048

GERP RS

3.8

Varity_R

0.062

gMVP

0.21

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over