Variant 11-63719914-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The ENST00000377819.10(RTN3):c.1412T>C(p.Val471Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.795 in 1,613,932 control chromosomes in the GnomAD database, including 516,213 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.73 ( 42226 hom., cov: 32)

Exomes 𝑓: 0.80 ( 473987 hom. )

Consequence

RTN3
ENST00000377819.10 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.0730

Variant links:

Genes affected

RTN3 (HGNC:10469): (reticulon 3) This gene belongs to the reticulon family of highly conserved genes that are preferentially expressed in neuroendocrine tissues. This family of proteins interact with, and modulate the activity of beta-amyloid converting enzyme 1 (BACE1), and the production of amyloid-beta. An increase in the expression of any reticulon protein substantially reduces the production of amyloid-beta, suggesting that reticulon proteins are negative modulators of BACE1 in cells. Alternatively spliced transcript variants encoding different isoforms have been found for this gene, and pseudogenes of this gene are located on chromosomes 4 and 12. [provided by RefSeq, May 2012]

RTN3 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=5.7710696E-7).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.963 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RTN3	NM_001265589.2 linkuse as main transcript	c.1412T>C	p.Val471Ala	missense_variant	3/9	ENST00000377819.10	NP_001252518.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RTN3	ENST00000377819.10 linkuse as main transcript	c.1412T>C	p.Val471Ala	missense_variant	3/9	1	NM_001265589.2	ENSP00000367050		O95197-1

Frequencies

GnomAD3 genomes

AF:

0.726

AC:

110409

AN:

151978

Hom.:

42216

Cov.:

show subpopulations

Gnomad AFR

AF:

0.468

Gnomad AMI

AF:

0.825

Gnomad AMR

AF:

0.845

Gnomad ASJ

AF:

0.753

Gnomad EAS

AF:

0.985

Gnomad SAS

AF:

0.721

Gnomad FIN

AF:

0.899

Gnomad MID

AF:

0.722

Gnomad NFE

AF:

0.807

Gnomad OTH

AF:

0.753

GnomAD3 exomes

AF:

0.806

AC:

202756

AN:

251410

Hom.:

83469

AF XY:

0.804

AC XY:

109184

AN XY:

135884

show subpopulations

Gnomad AFR exome

AF:

0.457

Gnomad AMR exome

AF:

0.901

Gnomad ASJ exome

AF:

0.765

Gnomad EAS exome

AF:

0.988

Gnomad SAS exome

AF:

0.727

Gnomad FIN exome

AF:

0.896

Gnomad NFE exome

AF:

0.807

Gnomad OTH exome

AF:

0.800

GnomAD4 exome

AF:

0.802

AC:

1172129

AN:

1461836

Hom.:

473987

Cov.:

AF XY:

0.800

AC XY:

581634

AN XY:

727222

show subpopulations

Gnomad4 AFR exome

AF:

0.449

Gnomad4 AMR exome

AF:

0.895

Gnomad4 ASJ exome

AF:

0.758

Gnomad4 EAS exome

AF:

0.989

Gnomad4 SAS exome

AF:

0.727

Gnomad4 FIN exome

AF:

0.891

Gnomad4 NFE exome

AF:

0.805

Gnomad4 OTH exome

AF:

0.792

GnomAD4 genome

AF:

0.726

AC:

110454

AN:

152096

Hom.:

42226

Cov.:

AF XY:

0.735

AC XY:

54676

AN XY:

74360

show subpopulations

Gnomad4 AFR

AF:

0.468

Gnomad4 AMR

AF:

0.845

Gnomad4 ASJ

AF:

0.753

Gnomad4 EAS

AF:

0.985

Gnomad4 SAS

AF:

0.721

Gnomad4 FIN

AF:

0.899

Gnomad4 NFE

AF:

0.807

Gnomad4 OTH

AF:

0.755

Alfa

AF:

0.793

Hom.:

117837

Bravo

AF:

0.714

TwinsUK

AF:

0.805

AC:

2986

ALSPAC

AF:

0.805

AC:

3103

ESP6500AA

AF:

0.480

AC:

2112

ESP6500EA

AF:

0.802

AC:

6891

ExAC

AF:

0.793

AC:

96343

Asia WGS

AF:

0.825

AC:

2869

AN:

3478

EpiCase

AF:

0.797

EpiControl

AF:

0.803

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.73

BayesDel_noAF

Benign

-0.68

CADD

Benign

2.9

DANN

Benign

0.53

DEOGEN2

Benign

0.020

T;.;.

Eigen

Benign

-1.3

Eigen_PC

Benign

-1.3

FATHMM_MKL

Benign

0.046

LIST_S2

Benign

0.34

T;T;T

MetaRNN

Benign

5.8e-7

T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.83

L;.;.

MutationTaster

Benign

1.0

P;P;P;P;P;P;P

PrimateAI

Benign

0.31

PROVEAN

Benign

-0.85

N;N;N

REVEL

Benign

0.031

Sift

Benign

0.56

T;T;T

Sift4G

Benign

0.49

T;T;T

Polyphen

0.0020

B;B;.

Vest4

0.020

MPC

0.069

ClinPred

0.0087

GERP RS

-2.9

Varity_R

0.034

gMVP

0.013

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over