Variant 11-63681666-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_ModerateBP6_Very_StrongBP7BS2

The ENST00000377819.10(RTN3):c.30C>T(p.Ser10=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00953 in 1,611,502 control chromosomes in the GnomAD database, including 101 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0077 ( 9 hom., cov: 32)

Exomes 𝑓: 0.0097 ( 92 hom. )

Consequence

RTN3
ENST00000377819.10 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.269

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 -15 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.29).

BP6

Variant 11-63681666-C-T is Benign according to our data. Variant chr11-63681666-C-T is described in ClinVar as [Benign]. Clinvar id is 777228.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.269 with no splicing effect.

BS2

High Homozygotes in GnomAd4 at 9 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RTN3	NM_001265589.2 linkuse as main transcript	c.30C>T	p.Ser10=	synonymous_variant	1/9	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.30C>T	p.Ser10=	synonymous_variant	1/9	1	NM_001265589.2	ENSP00000367050		O95197-1

Frequencies

GnomAD3 genomes

AF:

0.00775

AC:

1180

AN:

152270

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00224

Gnomad AMI

AF:

0.00110

Gnomad AMR

AF:

0.00850

Gnomad ASJ

AF:

0.0230

Gnomad EAS

AF:

0.000192

Gnomad SAS

AF:

0.000414

Gnomad FIN

AF:

0.00508

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.0117

Gnomad OTH

AF:

0.0100

GnomAD3 exomes

AF:

0.00786

AC:

1950

AN:

247996

Hom.:

AF XY:

0.00785

AC XY:

1056

AN XY:

134540

show subpopulations

Gnomad AFR exome

AF:

0.00159

Gnomad AMR exome

AF:

0.00547

Gnomad ASJ exome

AF:

0.0264

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000427

Gnomad FIN exome

AF:

0.00572

Gnomad NFE exome

AF:

0.0116

Gnomad OTH exome

AF:

0.00677

GnomAD4 exome

AF:

0.00972

AC:

14176

AN:

1459114

Hom.:

Cov.:

AF XY:

0.00946

AC XY:

6863

AN XY:

725696

show subpopulations

Gnomad4 AFR exome

AF:

0.00138

Gnomad4 AMR exome

AF:

0.00557

Gnomad4 ASJ exome

AF:

0.0227

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000674

Gnomad4 FIN exome

AF:

0.00626

Gnomad4 NFE exome

AF:

0.0111

Gnomad4 OTH exome

AF:

0.00901

GnomAD4 genome

AF:

0.00774

AC:

1179

AN:

152388

Hom.:

Cov.:

AF XY:

0.00696

AC XY:

519

AN XY:

74530

show subpopulations

Gnomad4 AFR

AF:

0.00224

Gnomad4 AMR

AF:

0.00849

Gnomad4 ASJ

AF:

0.0230

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.000414

Gnomad4 FIN

AF:

0.00508

Gnomad4 NFE

AF:

0.0117

Gnomad4 OTH

AF:

0.00992

Alfa

AF:

0.0101

Hom.:

Bravo

AF:

0.00739

Asia WGS

AF:

0.000577

AC:

AN:

3478

EpiCase

AF:

0.0109

EpiControl

AF:

0.0117

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jul 11, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.29

CADD

Benign

DANN

Benign

0.96

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

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