1-24535214-G-T

Variant names:

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

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001251982.1(RCAN3):​c.491G>T​(p.Arg164Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000696 in 1,436,828 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/17 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: not found (cov: 33)
  • Exomes 𝑓: 7.0e-7 (0 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.052915633).

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>T	p.Thr221Thr	synonymous	Exon 5 of 5	NP_038469.1	Q9UKA8-1
	RCAN3	NM_001251982.1		c.491G>T	p.Arg164Leu	missense	Exon 3 of 3	NP_001238911.1	Q9UKA8-3
	RCAN3	NM_001251985.1		c.317G>T	p.Arg106Leu	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>T	p.Arg164Leu	missense	Exon 3 of 3	ENSP00000391912.2	Q9UKA8-3
	RCAN3	ENST00000374393.4	TSL:1	c.317G>T	p.Arg106Leu	missense	Exon 2 of 2	ENSP00000363514.2	Q9UKA8-4
	RCAN3	ENST00000374395.9	TSL:1 MANE Select	c.663G>T	p.Thr221Thr	synonymous	Exon 5 of 5	ENSP00000363516.3	Q9UKA8-1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.96e-7 AC: 1 AN: 1436828 Hom.: 0 Cov.: 55 AF XY: 0.00 AC XY: 0 AN XY: 715054

African (AFR) AF: 0.00 AC: 0 AN: 31328

American (AMR) AF: 0.00 AC: 0 AN: 38600

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25700

East Asian (EAS) AF: 0.00 AC: 0 AN: 37304

South Asian (SAS) AF: 0.00 AC: 0 AN: 82574

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53232

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5694

European-Non Finnish (NFE) AF: 9.07e-7 AC: 1 AN: 1103018

Other (OTH) AF: 0.00 AC: 0 AN: 59378

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 63579

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.095
BayesDel_addAF	Benign	-0.11	T
BayesDel_noAF	Benign	-0.40
CADD	Benign	0.024
DANN	Benign	0.79
Eigen	Benign	-2.0
Eigen_PC	Benign	-2.2
FATHMM_MKL	Benign	0.075	N
LIST_S2	Benign	0.56	T
M_CAP	Benign	0.0055	T
MetaRNN	Benign	0.053	T
MetaSVM	Benign	-0.91	T
PhyloP100		-3.5
PROVEAN	Benign	0.68	N
REVEL	Benign	0.18
Sift	Uncertain	0.018	D
Sift4G	Uncertain	0.051	T
Vest4		0.13
MutPred		0.39		Loss of solvent accessibility (P = 0.0022)
MVP		0.34
ClinPred		0.099	T
GERP RS		-12
Mutation Taster		=96/4	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: rs196432; hg19: chr1-24861704;