rs196432

Variant names:

• chr1-24535214-G-A
• rs196432
• ENST00000412742.5:c.491G>A

Your query was ambiguous. Multiple possible variants found:

• chr1-24535214-G-A
• chr1-24535214-G-C
• chr1-24535214-G-T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001251982.1(RCAN3):​c.491G>A​(p.Arg164Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.476 in 1,588,326 control chromosomes in the GnomAD database, including 182,348 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/16 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.47 (16764 hom., cov: 33)
  • Exomes 𝑓: 0.48 (165584 hom.)
• Consequence: RCAN3 NM_001251982.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.51
• Publications: 28 publications found

Genes affected

RCAN3 (HGNC:3042): (RCAN family member 3) Enables phosphatase binding activity and troponin I binding activity. Predicted to be involved in calcium-mediated signaling. Predicted to be active in cytoplasm and nucleus. [provided by Alliance of Genome Resources, Apr 2022]

RCAN3AS (HGNC:39009): (RCAN3 antisense RNA)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=9.77613E-7).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.706 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001251982.1. 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
	RCAN3	NM_013441.4	MANE Select	c.663G>A	p.Thr221Thr	synonymous	Exon 5 of 5	NP_038469.1	Q9UKA8-1
	RCAN3	NM_001251982.1		c.491G>A	p.Arg164Gln	missense	Exon 3 of 3	NP_001238911.1	Q9UKA8-3
	RCAN3	NM_001251985.1		c.317G>A	p.Arg106Gln	missense	Exon 2 of 2	NP_001238914.1	Q9UKA8-4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RCAN3	ENST00000412742.5	TSL:1	c.491G>A	p.Arg164Gln	missense	Exon 3 of 3	ENSP00000391912.2	Q9UKA8-3
	RCAN3	ENST00000374393.4	TSL:1	c.317G>A	p.Arg106Gln	missense	Exon 2 of 2	ENSP00000363514.2	Q9UKA8-4
	RCAN3	ENST00000374395.9	TSL:1 MANE Select	c.663G>A	p.Thr221Thr	synonymous	Exon 5 of 5	ENSP00000363516.3	Q9UKA8-1

Frequencies

GnomAD3 genomes AF: 0.465 AC: 70702 AN: 151946 Hom.: 16755 Cov.: 33

Gnomad AFR AF: 0.460

Gnomad AMI AF: 0.462

Gnomad AMR AF: 0.387

Gnomad ASJ AF: 0.401

Gnomad EAS AF: 0.725

Gnomad SAS AF: 0.477

Gnomad FIN AF: 0.493

Gnomad MID AF: 0.357

Gnomad NFE AF: 0.467

Gnomad OTH AF: 0.415

GnomAD2 exomes AF: 0.472 AC: 106249 AN: 225008 AF XY: 0.472

Gnomad AFR exome AF: 0.462

Gnomad AMR exome AF: 0.376

Gnomad ASJ exome AF: 0.379

Gnomad EAS exome AF: 0.708

Gnomad FIN exome AF: 0.495

Gnomad NFE exome AF: 0.471

Gnomad OTH exome AF: 0.442

GnomAD4 exome AF: 0.477 AC: 684694 AN: 1436262 Hom.: 165584 Cov.: 55 AF XY: 0.475 AC XY: 339842 AN XY: 714754

African (AFR) AF: 0.456 AC: 14286 AN: 31298

American (AMR) AF: 0.381 AC: 14663 AN: 38496

Ashkenazi Jewish (ASJ) AF: 0.385 AC: 9878 AN: 25672

East Asian (EAS) AF: 0.737 AC: 27477 AN: 37270

South Asian (SAS) AF: 0.467 AC: 38520 AN: 82494

European-Finnish (FIN) AF: 0.498 AC: 26484 AN: 53224

Middle Eastern (MID) AF: 0.377 AC: 2147 AN: 5692

European-Non Finnish (NFE) AF: 0.474 AC: 523012 AN: 1102756

Other (OTH) AF: 0.476 AC: 28227 AN: 59360

GnomAD4 genome AF: 0.465 AC: 70735 AN: 152064 Hom.: 16764 Cov.: 33 AF XY: 0.464 AC XY: 34510 AN XY: 74326

African (AFR) AF: 0.459 AC: 19041 AN: 41468

American (AMR) AF: 0.387 AC: 5910 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.401 AC: 1388 AN: 3464

East Asian (EAS) AF: 0.726 AC: 3752 AN: 5170

South Asian (SAS) AF: 0.479 AC: 2311 AN: 4824

European-Finnish (FIN) AF: 0.493 AC: 5210 AN: 10570

Middle Eastern (MID) AF: 0.349 AC: 102 AN: 292

European-Non Finnish (NFE) AF: 0.467 AC: 31712 AN: 67966

Other (OTH) AF: 0.421 AC: 889 AN: 2112

Alfa AF: 0.464 Hom.: 63579

Bravo AF: 0.459

TwinsUK AF: 0.475 AC: 1761

ALSPAC AF: 0.473 AC: 1822

ESP6500AA AF: 0.464 AC: 2045

ESP6500EA AF: 0.461 AC: 3966

ExAC AF: 0.481 AC: 58383

Asia WGS AF: 0.642 AC: 2231 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.075
BayesDel_addAF	Benign	-0.57	T
BayesDel_noAF	Benign	-0.45
CADD	Benign	0.068
DANN	Benign	0.87
Eigen	Benign	-2.2
Eigen_PC	Benign	-2.3
FATHMM_MKL	Benign	0.036	N
LIST_S2	Benign	0.55	T
MetaRNN	Benign	9.8e-7	T
MetaSVM	Benign	-1.0	T
PhyloP100		-3.5
PROVEAN	Benign	0.68	N
REVEL	Benign	0.039
Sift	Benign	1.0	T
Sift4G	Benign	0.84	T
Vest4		0.10
ClinPred		0.013	T
GERP RS		-12
Mutation Taster		=98/2	polymorphism (auto)

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: rs196432; hg19: chr1-24861704; COSMIC: COSV65558435; COSMIC: COSV65558435;