dbSNP rs772398158: RCN1:p.Arg114Ser (chr11-32097231-A-T) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_002901.4(RCN1):c.342A>T(p.Arg114Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000227 in 1,456,626 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 30)

Exomes 𝑓: 0.000023 ( 0 hom. )

Consequence

RCN1
NM_002901.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.08

Publications

0 publications found

Variant links:

Genes affected

RCN1 (HGNC:9934): (reticulocalbin 1) Reticulocalbin 1 is a calcium-binding protein located in the lumen of the ER. The protein contains six conserved regions with similarity to a high affinity Ca(+2)-binding motif, the EF-hand. High conservation of amino acid residues outside of these motifs, in comparison to mouse reticulocalbin, is consistent with a possible biochemical function besides that of calcium binding. In human endothelial and prostate cancer cell lines this protein localizes to the plasma membrane.[provided by RefSeq, Jan 2009]

RCN1 links:

ENSG00000285283 (HGNC:):

ENSG00000285283 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RCN1	NM_002901.4 link	c.342A>T	p.Arg114Ser	missense_variant	Exon 2 of 6	ENST00000054950.4	NP_002892.1	Q15293-1V9HW95

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RCN1	ENST00000054950.4 link	c.342A>T	p.Arg114Ser	missense_variant	Exon 2 of 6	1	NM_002901.4	ENSP00000054950.4		Q15293-1
ENSG00000285283	ENST00000532942.5 link	c.189A>T	p.Arg63Ser	missense_variant	Exon 2 of 6	2		ENSP00000436422.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.0000412

AC:

AN:

242918

AF XY:

0.0000457

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000305

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000227

AC:

AN:

1456626

Hom.:

Cov.:

AF XY:

0.0000262

AC XY:

AN XY:

724442

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33174

American (AMR)

AF:

0.00

AC:

AN:

43424

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25962

East Asian (EAS)

AF:

0.00

AC:

AN:

39626

South Asian (SAS)

AF:

0.000271

AC:

AN:

84764

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53348

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5746

European-Non Finnish (NFE)

AF:

0.00000901

AC:

AN:

1110436

Other (OTH)

AF:

0.00

AC:

AN:

60146

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.454

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000756

ExAC

AF:

0.0000412

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Jul 25, 2024

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The c.342A>T (p.R114S) alteration is located in exon 2 (coding exon 2) of the RCN1 gene. This alteration results from a A to T substitution at nucleotide position 342, causing the arginine (R) at amino acid position 114 to be replaced by a serine (S). 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

Pathogenic

0.98

BayesDel_addAF

Uncertain

0.082

BayesDel_noAF

Pathogenic

0.18

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.24

.;T

Eigen

Benign

0.17

Eigen_PC

Benign

0.16

FATHMM_MKL

Benign

0.71

LIST_S2

Uncertain

0.88

D;D

M_CAP

Uncertain

0.15

MetaRNN

Uncertain

0.71

D;D

MetaSVM

Benign

-0.46

MutationAssessor

Uncertain

2.3

.;M

PhyloP100

1.1

PrimateAI

Uncertain

0.77

PROVEAN

Pathogenic

-4.7

D;D

REVEL

Uncertain

0.49

Sift

Uncertain

0.0010

D;D

Sift4G

Uncertain

0.0020

D;D

Polyphen

0.53

.;P

Vest4

0.83

MutPred

0.55

.;Loss of MoRF binding (P = 0.0508);

MVP

0.82

MPC

1.1

ClinPred

0.47

GERP RS

2.7

Varity_R

0.84

gMVP

0.69

Mutation Taster

=13/87

disease causing

(source)

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

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rs772398158

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over