Variant 19-49542565-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The ENST00000270645.8(RCN3):c.692C>T(p.Ser231Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000207 in 1,447,426 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: not found (cov: 32)

Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

RCN3
ENST00000270645.8 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.22

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:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.13121068).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RCN3	NM_020650.3 linkuse as main transcript	c.692C>T	p.Ser231Leu	missense_variant	6/7	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.692C>T	p.Ser231Leu	missense_variant	6/7	1	NM_020650.3	ENSP00000270645.2	Q96D15
RCN3	ENST00000598833.1 linkuse as main transcript	c.466-4256C>T		intron_variant		3		ENSP00000470540.1	M0QZH0
RCN3	ENST00000593483.1 linkuse as main transcript	c.-38C>T		upstream_gene_variant		5		ENSP00000470771.1	M0QZU3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000207

AC:

AN:

1447426

Hom.:

Cov.:

AF XY:

0.00000278

AC XY:

AN XY:

718428

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

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:

0.00000271

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

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

Dec 14, 2023

The c.692C>T (p.S231L) alteration is located in exon 6 (coding exon 5) of the RCN3 gene. This alteration results from a C to T substitution at nucleotide position 692, causing the serine (S) at amino acid position 231 to be replaced by a leucine (L). 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

0.15

BayesDel_addAF

Benign

-0.17

BayesDel_noAF

Benign

-0.48

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.028

Eigen

Benign

-0.46

Eigen_PC

Benign

-0.45

FATHMM_MKL

Benign

0.49

LIST_S2

Uncertain

0.88

M_CAP

Benign

0.017

MetaRNN

Benign

0.13

MetaSVM

Benign

-0.99

MutationAssessor

Uncertain

2.1

MutationTaster

Benign

1.0

PrimateAI

Benign

0.47

PROVEAN

Uncertain

-3.3

REVEL

Benign

0.080

Sift

Benign

0.052

Sift4G

Benign

0.16

Polyphen

0.041

Vest4

0.33

MutPred

0.41

Gain of catalytic residue at S231 (P = 0.0047);

MVP

0.60

MPC

0.017

ClinPred

0.32

GERP RS

5.2

RBP_binding_hub_radar

0.92

RBP_regulation_power_radar

2.0

Varity_R

0.15

gMVP

0.39

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over