dbSNP rs764690503: RCAN3:p.Ala163Glu (chr1-24533201-C-A) – ACMG Classification: Uncertain_significance (3 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2PP3

The NM_013441.4(RCAN3):c.488C>A(p.Ala163Glu) variant causes a missense change. The variant allele was found at a frequency of 0.000000688 in 1,453,464 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic 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. A163V) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

RCAN3
NM_013441.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 5.86

Publications

0 publications found

Variant links:

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]

RCAN3 links:

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

RCAN3AS links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.756

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_013441.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
RCAN3	NM_013441.4	MANE Select	c.488C>A	p.Ala163Glu	missense	Exon 4 of 5	NP_038469.1	Q9UKA8-1
RCAN3	NM_001251977.2		c.488C>A	p.Ala163Glu	missense	Exon 4 of 5	NP_001238906.1	Q9UKA8-1
RCAN3	NM_001251978.1		c.488C>A	p.Ala163Glu	missense	Exon 4 of 5	NP_001238907.1	Q9UKA8-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
RCAN3	ENST00000374395.9	TSL:1 MANE Select	c.488C>A	p.Ala163Glu	missense	Exon 4 of 5	ENSP00000363516.3	Q9UKA8-1
RCAN3	ENST00000538532.6	TSL:1	c.488C>A	p.Ala163Glu	missense	Exon 4 of 5	ENSP00000445401.2	Q9UKA8-1
RCAN3	ENST00000630217.2	TSL:1	c.314C>A	p.Ala105Glu	missense	Exon 3 of 4	ENSP00000486836.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.88e-7

AC:

AN:

1453464

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

722968

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

32972

American (AMR)

AF:

0.00

AC:

AN:

42850

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25910

East Asian (EAS)

AF:

0.00

AC:

AN:

38824

South Asian (SAS)

AF:

0.00

AC:

AN:

84874

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53318

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5746

European-Non Finnish (NFE)

AF:

9.02e-7

AC:

AN:

1109000

Other (OTH)

AF:

0.00

AC:

AN:

59970

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.575

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.38

BayesDel_addAF

Pathogenic

0.16

BayesDel_noAF

Uncertain

0.0

CADD

Uncertain

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.19

Eigen

Uncertain

0.22

Eigen_PC

Benign

0.12

FATHMM_MKL

Pathogenic

0.97

LIST_S2

Uncertain

0.95

M_CAP

Benign

0.055

MetaRNN

Pathogenic

0.76

MetaSVM

Benign

-0.82

MutationAssessor

Uncertain

2.2

PhyloP100

5.9

PrimateAI

Uncertain

0.65

PROVEAN

Uncertain

-3.6

REVEL

Uncertain

0.32

Sift

Uncertain

0.016

Sift4G

Benign

0.12

Polyphen

0.99

Vest4

0.71

MutPred

0.57

Gain of disorder (P = 0.0382)

MVP

0.64

MPC

0.85

ClinPred

0.98

GERP RS

4.5

Varity_R

0.53

gMVP

0.57

Mutation Taster

=60/40

polymorphism

(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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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over