Variant 19-49534351-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The ENST00000270645.8(RCN3):c.401G>C(p.Gly134Ala) variant causes a missense change. The variant allele was found at a frequency of 0.00154 in 1,534,872 control chromosomes in the GnomAD database, including 3 homozygotes. 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 0.00078 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0016 ( 3 hom. )

Consequence

RCN3
ENST00000270645.8 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.62

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:

RCN3 (HGNC:):

RCN3 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.06481987).

BS2

High Homozygotes in GnomAdExome4 at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RCN3	NM_020650.3 linkuse as main transcript	c.401G>C	p.Gly134Ala	missense_variant	3/7	ENST00000270645.8	NP_065701.2	Q96D15

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
RCN3	ENST00000270645.8 linkuse as main transcript	c.401G>C	p.Gly134Ala	missense_variant	3/7	1	NM_020650.3	ENSP00000270645.2	Q96D15
RCN3	ENST00000598833.1 linkuse as main transcript	c.248G>C	p.Gly83Ala	missense_variant	2/4	3		ENSP00000470540.1	M0QZH0
RCN3	ENST00000597801.1 linkuse as main transcript	c.351+50G>C		intron_variant		5		ENSP00000469727.1	M0QYB8
RCN3	ENST00000593644.1 linkuse as main transcript	n.172-2682G>C		intron_variant		3

Frequencies

GnomAD3 genomes

AF:

0.000775

AC:

118

AN:

152164

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000338

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000262

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.0000941

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00146

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000679

AC:

AN:

129560

Hom.:

AF XY:

0.000685

AC XY:

AN XY:

70038

show subpopulations

Gnomad AFR exome

AF:

0.000334

Gnomad AMR exome

AF:

0.0000879

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000162

Gnomad NFE exome

AF:

0.00168

Gnomad OTH exome

AF:

0.000789

GnomAD4 exome

AF:

0.00162

AC:

2239

AN:

1382708

Hom.:

Cov.:

AF XY:

0.00158

AC XY:

1079

AN XY:

682312

show subpopulations

Gnomad4 AFR exome

AF:

0.000301

Gnomad4 AMR exome

AF:

0.0000593

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000128

Gnomad4 FIN exome

AF:

0.000239

Gnomad4 NFE exome

AF:

0.00203

Gnomad4 OTH exome

AF:

0.000697

GnomAD4 genome

AF:

0.000775

AC:

118

AN:

152164

Hom.:

Cov.:

AF XY:

0.000767

AC XY:

AN XY:

74326

show subpopulations

Gnomad4 AFR

AF:

0.000338

Gnomad4 AMR

AF:

0.000262

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.0000941

Gnomad4 NFE

AF:

0.00146

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.00121

Hom.:

Bravo

AF:

0.000695

TwinsUK

AF:

0.00108

AC:

ALSPAC

AF:

0.00208

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000599

AC:

ExAC

AF:

0.000256

AC:

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 13, 2022

The c.401G>C (p.G134A) alteration is located in exon 3 (coding exon 2) of the RCN3 gene. This alteration results from a G to C substitution at nucleotide position 401, causing the glycine (G) at amino acid position 134 to be replaced by an alanine (A). 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

0.11

BayesDel_addAF

Benign

-0.47

BayesDel_noAF

Benign

-0.45

CADD

Uncertain

DANN

Uncertain

0.98

DEOGEN2

Benign

0.0021

T;.

Eigen

Benign

-0.24

Eigen_PC

Benign

-0.045

FATHMM_MKL

Benign

0.37

LIST_S2

Benign

0.82

T;T

M_CAP

Benign

0.058

MetaRNN

Benign

0.065

T;T

MetaSVM

Benign

-0.88

MutationAssessor

Benign

0.26

N;.

MutationTaster

Benign

0.98

PrimateAI

Uncertain

0.77

PROVEAN

Benign

-0.12

N;.

REVEL

Benign

0.12

Sift

Benign

0.096

T;.

Sift4G

Benign

0.19

T;T

Polyphen

0.11

B;.

Vest4

0.12

MVP

0.66

MPC

0.86

ClinPred

0.020

GERP RS

3.5

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.086

gMVP

0.61

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