rs574595817

Variant names:

• chr19-49534309-C-A
• rs574595817
• NM_020650.3:c.359C>A

Your query was ambiguous. Multiple possible variants found:

• chr19-49534309-C-A
• chr19-49534309-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_020650.3(RCN3):​c.359C>A​(p.Ala120Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000746 in 1,340,670 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A120V) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 7.5e-7 (0 hom.)
• Consequence: RCN3 NM_020650.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.926
• 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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.14413887).

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.359C>A	p.Ala120Glu	missense	Exon 3 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.359C>A	p.Ala120Glu	missense	Exon 3 of 7	ENSP00000270645.2	Q96D15
	RCN3	ENST00000892641.1		c.359C>A	p.Ala120Glu	missense	Exon 3 of 7	ENSP00000562700.1
	RCN3	ENST00000956869.1		c.359C>A	p.Ala120Glu	missense	Exon 2 of 6	ENSP00000626928.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 7.46e-7 AC: 1 AN: 1340670 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 658608

African (AFR) AF: 0.00 AC: 0 AN: 27732

American (AMR) AF: 0.00 AC: 0 AN: 27406

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 20972

East Asian (EAS) AF: 0.00 AC: 0 AN: 32970

South Asian (SAS) AF: 0.00 AC: 0 AN: 71228

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 44598

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5252

European-Non Finnish (NFE) AF: 9.48e-7 AC: 1 AN: 1054926

Other (OTH) AF: 0.00 AC: 0 AN: 55586

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.16
BayesDel_addAF	Benign	-0.13	T
BayesDel_noAF	Benign	-0.42
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Benign	0.0011	T
Eigen	Benign	-0.46
Eigen_PC	Benign	-0.34
FATHMM_MKL	Benign	0.087	N
LIST_S2	Benign	0.68	T
M_CAP	Benign	0.055	D
MetaRNN	Benign	0.14	T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	0.23	N
PhyloP100		0.93
PrimateAI	Pathogenic	0.85	D
PROVEAN	Benign	0.53	N
REVEL	Benign	0.096
Sift	Benign	0.099	T
Sift4G	Benign	0.14	T
Polyphen		0.42	B
Vest4		0.27
MutPred		0.42		Gain of disorder (P = 0.0436)
MVP		0.64
MPC		0.85
ClinPred		0.35	T
GERP RS		2.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.22
gMVP		0.32
Mutation Taster		=92/8	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

dbSNP: rs574595817; hg19: chr19-50037566;