chr1-24533201-C-A

Variant names:

• chr1-24533201-C-A
• NM_013441.4:c.488C>A

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP3

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.86

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

Verdict is Uncertain_significance. Variant got 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.756

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RCAN3	NM_013441.4	c.488C>A	p.Ala163Glu	missense_variant	Exon 4 of 5	ENST00000374395.9	NP_038469.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RCAN3	ENST00000374395.9	c.488C>A	p.Ala163Glu	missense_variant	Exon 4 of 5	1	NM_013441.4	ENSP00000363516.3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.88e-7 AC: 1 AN: 1453464 Hom.: 0 Cov.: 32 AF XY: 0.00000138 AC XY: 1 AN XY: 722968

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 9.02e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.38
BayesDel_addAF	Pathogenic	0.16	D
BayesDel_noAF	Uncertain	0.0
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Benign	0.19	.;T;.;.;T;.;T;.
Eigen	Uncertain	0.22
Eigen_PC	Benign	0.12
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Uncertain	0.95	.;.;D;D;.;D;D;.
M_CAP	Benign	0.055	D
MetaRNN	Pathogenic	0.76	D;D;D;D;D;D;D;D
MetaSVM	Benign	-0.82	T
MutationAssessor	Uncertain	2.2	.;M;.;.;M;.;M;.
PrimateAI	Uncertain	0.65	T
PROVEAN	Uncertain	-3.6	.;.;.;.;D;.;.;.
REVEL	Uncertain	0.32
Sift	Uncertain	0.016	.;.;.;.;D;.;.;.
Sift4G	Benign	0.12	T;T;T;T;T;T;T;T
Polyphen		0.99, 1.0	.;D;.;.;D;D;D;.
Vest4		0.71
MutPred		0.57		.;Gain of disorder (P = 0.0382);.;.;Gain of disorder (P = 0.0382);.;Gain of disorder (P = 0.0382);.;
MVP		0.64
MPC		0.85
ClinPred		0.98	D
GERP RS		4.5
Varity_R		0.53
gMVP		0.57

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr1-24859691;