1-24531284-A-G

Position:

• chr1-24531284-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_001251983.2(RCAN3):​c.-114A>G variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 31)
• Consequence: RCAN3 NM_001251983.2 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.108

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:):

ACMG classification

Verdict is Uncertain_significance. Variant got 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.906

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RCAN3	NM_013441.4	c.262A>G	p.Arg88Gly	missense_variant	3/5	ENST00000374395.9	NP_038469.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RCAN3	ENST00000374395.9	c.262A>G	p.Arg88Gly	missense_variant	3/5	1	NM_013441.4	ENSP00000363516.3

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 31

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Mar 06, 2023

The c.262A>G (p.R88G) alteration is located in exon 3 (coding exon 2) of the RCAN3 gene. This alteration results from a A to G substitution at nucleotide position 262, causing the arginine (R) at amino acid position 88 to be replaced by a glycine (G). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.40
BayesDel_addAF	Pathogenic	0.23	D
BayesDel_noAF	Uncertain	0.090
CADD	Benign	21
DANN	Uncertain	0.99
DEOGEN2	Benign	0.32	T;T;.;T;.
Eigen	Benign	-0.49
Eigen_PC	Benign	-0.58
FATHMM_MKL	Benign	0.65	D
LIST_S2	Uncertain	0.96	.;.;D;D;D
M_CAP	Uncertain	0.091	D
MetaRNN	Pathogenic	0.91	D;D;D;D;D
MetaSVM	Benign	-0.59	T
MutationAssessor	Uncertain	2.4	M;M;M;M;M
PrimateAI	Pathogenic	0.80	D
PROVEAN	Pathogenic	-6.1	.;D;.;.;D
REVEL	Uncertain	0.46
Sift	Uncertain	0.0010	.;D;.;.;D
Sift4G	Pathogenic	0.0010	D;D;D;D;D
Polyphen		0.70	P;P;P;P;.
Vest4		0.90
MutPred		0.77		Loss of stability (P = 0.0297);Loss of stability (P = 0.0297);Loss of stability (P = 0.0297);Loss of stability (P = 0.0297);Loss of stability (P = 0.0297);
MVP		0.51
MPC		0.88
ClinPred		1.0	D
GERP RS		-5.0
Varity_R		0.81
gMVP		0.72

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr1-24857774;