chr19-49537138-C-T

Variant names:

• chr19-49537138-C-T
• NM_020650.3:c.551C>T

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_020650.3(RCN3):​c.551C>T​(p.Thr184Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: RCN3 NM_020650.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.16
• Publications: 0 publications found

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]

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_020650.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RCN3	NM_020650.3	MANE Select	c.551C>T	p.Thr184Ile	missense	Exon 4 of 7	NP_065701.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RCN3	ENST00000270645.8	TSL:1 MANE Select	c.551C>T	p.Thr184Ile	missense	Exon 4 of 7	ENSP00000270645.2	Q96D15
	RCN3	ENST00000892641.1		c.551C>T	p.Thr184Ile	missense	Exon 4 of 7	ENSP00000562700.1
	RCN3	ENST00000956869.1		c.551C>T	p.Thr184Ile	missense	Exon 3 of 6	ENSP00000626928.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1444502 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 717986

African (AFR) AF: 0.00 AC: 0 AN: 32360

American (AMR) AF: 0.00 AC: 0 AN: 42946

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25696

East Asian (EAS) AF: 0.00 AC: 0 AN: 37958

South Asian (SAS) AF: 0.00 AC: 0 AN: 84486

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53176

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5720

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1102684

Other (OTH) AF: 0.00 AC: 0 AN: 59476

GnomAD4 genome Cov.: 31

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.85
BayesDel_addAF	Pathogenic	0.27	D
BayesDel_noAF	Pathogenic	0.15
CADD	Pathogenic	26
DANN	Uncertain	1.0
DEOGEN2	Benign	0.26	T
Eigen	Uncertain	0.62
Eigen_PC	Uncertain	0.56
FATHMM_MKL	Uncertain	0.91	D
LIST_S2	Uncertain	0.94	D
M_CAP	Uncertain	0.11	D
MetaRNN	Uncertain	0.62	D
MetaSVM	Uncertain	0.0024	D
MutationAssessor	Pathogenic	3.4	M
PhyloP100		3.2
PrimateAI	Uncertain	0.56	T
PROVEAN	Pathogenic	-4.8	D
REVEL	Uncertain	0.42
Sift	Uncertain	0.0020	D
Sift4G	Uncertain	0.0030	D
Polyphen		0.98	D
Vest4		0.78
MutPred		0.36		Loss of phosphorylation at T184 (P = 0.0344)
MVP		0.93
MPC		1.5
ClinPred		0.99	D
GERP RS		5.0
Varity_R		0.70
gMVP		0.76
Mutation Taster		=81/19	polymorphism

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

Other links and lift over

hg19: chr19-50040395; COSMIC: COSV54543255; COSMIC: COSV54543255;