rs141528253

Variant names:

• chr19-49537091-C-T
• rs141528253
• NM_020650.3:c.504C>T

Your query was ambiguous. Multiple possible variants found:

• chr19-49537091-C-T
• chr19-49537091-C-G

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_Strong BP6_Moderate BP7 BS2

The NM_020650.3(RCN3):​c.504C>T​(p.Asp168Asp) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0042 in 1,595,492 control chromosomes in the GnomAD database, including 29 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0035 (2 hom., cov: 31)
  • Exomes 𝑓: 0.0043 (27 hom.)
• Consequence: RCN3 NM_020650.3 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -2.38
• Publications: 2 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: Benign. The variant received -11 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.007635653).
• BP6: Variant 19-49537091-C-T is Benign according to our data. Variant chr19-49537091-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 2650250.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-2.38 with no splicing effect.
• BS2: High Homozygotes in GnomAd4 at 2 AR gene

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.504C>T	p.Asp168Asp	synonymous	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.504C>T	p.Asp168Asp	synonymous	Exon 4 of 7	ENSP00000270645.2	Q96D15
	RCN3	ENST00000597801.1	TSL:5	c.410C>T	p.Thr137Met	missense	Exon 4 of 4	ENSP00000469727.1	M0QYB8
	RCN3	ENST00000892641.1		c.504C>T	p.Asp168Asp	synonymous	Exon 4 of 7	ENSP00000562700.1

Frequencies

GnomAD3 genomes AF: 0.00346 AC: 526 AN: 152174 Hom.: 2 Cov.: 31

Gnomad AFR AF: 0.000772

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00393

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00135

Gnomad SAS AF: 0.000621

Gnomad FIN AF: 0.00594

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.00517

Gnomad OTH AF: 0.00335

GnomAD2 exomes AF: 0.00389 AC: 925 AN: 237804 AF XY: 0.00410

Gnomad AFR exome AF: 0.000793

Gnomad AMR exome AF: 0.00235

Gnomad ASJ exome AF: 0.000416

Gnomad EAS exome AF: 0.000847

Gnomad FIN exome AF: 0.00448

Gnomad NFE exome AF: 0.00641

Gnomad OTH exome AF: 0.00390

GnomAD4 exome AF: 0.00428 AC: 6178 AN: 1443200 Hom.: 27 Cov.: 30 AF XY: 0.00423 AC XY: 3037 AN XY: 717206

African (AFR) AF: 0.000680 AC: 22 AN: 32356

American (AMR) AF: 0.00277 AC: 119 AN: 42902

Ashkenazi Jewish (ASJ) AF: 0.000235 AC: 6 AN: 25552

East Asian (EAS) AF: 0.000237 AC: 9 AN: 37896

South Asian (SAS) AF: 0.000297 AC: 25 AN: 84304

European-Finnish (FIN) AF: 0.00436 AC: 232 AN: 53162

Middle Eastern (MID) AF: 0.00246 AC: 14 AN: 5700

European-Non Finnish (NFE) AF: 0.00506 AC: 5570 AN: 1101854

Other (OTH) AF: 0.00304 AC: 181 AN: 59474

GnomAD4 genome AF: 0.00345 AC: 526 AN: 152292 Hom.: 2 Cov.: 31 AF XY: 0.00334 AC XY: 249 AN XY: 74458

African (AFR) AF: 0.000770 AC: 32 AN: 41580

American (AMR) AF: 0.00392 AC: 60 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00135 AC: 7 AN: 5176

South Asian (SAS) AF: 0.000621 AC: 3 AN: 4830

European-Finnish (FIN) AF: 0.00594 AC: 63 AN: 10610

Middle Eastern (MID) AF: 0.00680 AC: 2 AN: 294

European-Non Finnish (NFE) AF: 0.00517 AC: 352 AN: 68020

Other (OTH) AF: 0.00331 AC: 7 AN: 2114

Alfa AF: 0.00376 Hom.: 1

Bravo AF: 0.00330

TwinsUK AF: 0.00620 AC: 23

ALSPAC AF: 0.00519 AC: 20

ESP6500AA AF: 0.000908 AC: 4

ESP6500EA AF: 0.00570 AC: 49

ExAC AF: 0.00446 AC: 542

Asia WGS AF: 0.000866 AC: 3 AN: 3478

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.15
BayesDel_addAF	Benign	-0.50	T
BayesDel_noAF	Benign	-0.48
CADD	Benign	1.9
DANN	Benign	0.64
DEOGEN2	Benign	0.0061	T
FATHMM_MKL	Benign	0.066	N
LIST_S2	Benign	0.29	T
MetaRNN	Benign	0.0076	T
PhyloP100		-2.4
Sift4G	Uncertain	0.048	D
MVP		0.48
GERP RS		-1.1
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=97/3	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: rs141528253; hg19: chr19-50040348;