Variant 19-49537091-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_StrongBP6_ModerateBP7BS2

The NM_020650.3(RCN3):c.504C>T(p.Asp168=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0042 in 1,595,492 control chromosomes in the GnomAD database, including 29 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0035 ( 2 hom., cov: 31)

Exomes 𝑓: 0.0043 ( 27 hom. )

Consequence

RCN3
NM_020650.3 synonymous

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -2.38

Variant links:

Genes affected

RCN3 (HGNC:21145): (reticulocalbin 3) Enables calcium ion binding activity. Involved in several processes, including collagen biosynthetic process; positive regulation of peptidase activity; and regulation of protein kinase B signaling. Located in endoplasmic reticulum. [provided by Alliance of Genome Resources, Apr 2022]

RCN3 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -11 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.007635653).

BP6

Variant 19-49537091-C-T is Benign according to our data. Variant chr19-49537091-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 2650250.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=-2.38 with no splicing effect.

BS2

High Homozygotes in GnomAd4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RCN3	NM_020650.3 linkuse as main transcript	c.504C>T	p.Asp168=	synonymous_variant	4/7	ENST00000270645.8	NP_065701.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris
RCN3	ENST00000270645.8 linkuse as main transcript	c.504C>T	p.Asp168=	synonymous_variant	4/7	1	NM_020650.3	ENSP00000270645	P1
RCN3	ENST00000597801.1 linkuse as main transcript	c.410C>T	p.Thr137Met	missense_variant	4/4	5		ENSP00000469727
RCN3	ENST00000598833.1 linkuse as main transcript	c.351C>T	p.Asp117=	synonymous_variant	3/4	3		ENSP00000470540
RCN3	ENST00000593644.1 linkuse as main transcript			downstream_gene_variant		3

Frequencies

GnomAD3 genomes

AF:

0.00346

AC:

526

AN:

152174

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000772

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00393

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00135

Gnomad SAS

AF:

0.000621

Gnomad FIN

AF:

0.00594

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.00517

Gnomad OTH

AF:

0.00335

GnomAD3 exomes

AF:

0.00389

AC:

925

AN:

237804

Hom.:

AF XY:

0.00410

AC XY:

529

AN XY:

128998

show subpopulations

Gnomad AFR exome

AF:

0.000793

Gnomad AMR exome

AF:

0.00235

Gnomad ASJ exome

AF:

0.000416

Gnomad EAS exome

AF:

0.000847

Gnomad SAS exome

AF:

0.000208

Gnomad FIN exome

AF:

0.00448

Gnomad NFE exome

AF:

0.00641

Gnomad OTH exome

AF:

0.00390

GnomAD4 exome

AF:

0.00428

AC:

6178

AN:

1443200

Hom.:

Cov.:

AF XY:

0.00423

AC XY:

3037

AN XY:

717206

show subpopulations

Gnomad4 AFR exome

AF:

0.000680

Gnomad4 AMR exome

AF:

0.00277

Gnomad4 ASJ exome

AF:

0.000235

Gnomad4 EAS exome

AF:

0.000237

Gnomad4 SAS exome

AF:

0.000297

Gnomad4 FIN exome

AF:

0.00436

Gnomad4 NFE exome

AF:

0.00506

Gnomad4 OTH exome

AF:

0.00304

GnomAD4 genome

AF:

0.00345

AC:

526

AN:

152292

Hom.:

Cov.:

AF XY:

0.00334

AC XY:

249

AN XY:

74458

show subpopulations

Gnomad4 AFR

AF:

0.000770

Gnomad4 AMR

AF:

0.00392

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00135

Gnomad4 SAS

AF:

0.000621

Gnomad4 FIN

AF:

0.00594

Gnomad4 NFE

AF:

0.00517

Gnomad4 OTH

AF:

0.00331

Alfa

AF:

0.00376

Hom.:

Bravo

AF:

0.00330

TwinsUK

AF:

0.00620

AC:

ALSPAC

AF:

0.00519

AC:

ESP6500AA

AF:

0.000908

AC:

ESP6500EA

AF:

0.00570

AC:

ExAC

AF:

0.00446

AC:

542

Asia WGS

AF:

0.000866

AC:

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Oct 01, 2022

RCN3: BP4, BP7 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.50

BayesDel_noAF

Benign

-0.48

CADD

Benign

1.9

DANN

Benign

0.64

DEOGEN2

Benign

0.0061

FATHMM_MKL

Benign

0.066

LIST_S2

Benign

0.29

MetaRNN

Benign

0.0076

MutationTaster

Benign

1.0

Sift4G

Uncertain

0.048

MVP

0.48

GERP RS

-1.1

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