rs200182913

Variant names:

• chr10-66520698-G-A
• rs200182913
• NM_013266.4:c.1450C>T

Your query was ambiguous. Multiple possible variants found:

• chr10-66520698-G-A
• chr10-66520698-G-C
• chr10-66520698-G-T

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_013266.4(CTNNA3):​c.1450C>T​(p.Arg484Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000633 in 1,611,052 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R484H) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.000086 (0 hom., cov: 31)
  • Exomes 𝑓: 0.000061 (0 hom.)
• Consequence: CTNNA3 NM_013266.4 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.68
• Publications: 6 publications found

Genes affected

CTNNA3 (HGNC:2511): (catenin alpha 3) This gene encodes a protein that belongs to the vinculin/alpha-catenin family. The encoded protein plays a role in cell-cell adhesion in muscle cells. Mutations in this gene are associated with arrhythmogenic right ventricular dysplasia, familial 13. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Mar 2014]

CTNNA3 Gene-Disease associations (from GenCC):

• arrhythmogenic right ventricular cardiomyopathy

  Inheritance: AD Classification: LIMITED Submitted by: ClinGen
• arrhythmogenic right ventricular dysplasia 13

  Inheritance: AD Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics
• congenital heart disease

  Inheritance: Unknown Classification: NO_KNOWN Submitted by: ClinGen

ENSG00000298814 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -10 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.012717605).
• BP6: Variant 10-66520698-G-A is Benign according to our data. Variant chr10-66520698-G-A is described in ClinVar as Likely_benign. ClinVar VariationId is 415376.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High AC in GnomAd4 at 13 AD,Unknown gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_013266.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CTNNA3	NM_013266.4	MANE Select	c.1450C>T	p.Arg484Cys	missense	Exon 11 of 18	NP_037398.2
	CTNNA3	NM_001127384.3		c.1450C>T	p.Arg484Cys	missense	Exon 11 of 18	NP_001120856.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CTNNA3	ENST00000433211.7	TSL:1 MANE Select	c.1450C>T	p.Arg484Cys	missense	Exon 11 of 18	ENSP00000389714.1
	CTNNA3	ENST00000682758.1		c.1450C>T	p.Arg484Cys	missense	Exon 12 of 19	ENSP00000508047.1
	CTNNA3	ENST00000684154.1		c.1450C>T	p.Arg484Cys	missense	Exon 11 of 18	ENSP00000508371.1

Frequencies

GnomAD3 genomes AF: 0.0000856 AC: 13 AN: 151872 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000657

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00212

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.000480

GnomAD2 exomes AF: 0.000254 AC: 63 AN: 248520 AF XY: 0.000253

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000891

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00308

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000610 AC: 89 AN: 1459064 Hom.: 0 Cov.: 30 AF XY: 0.0000606 AC XY: 44 AN XY: 725928

African (AFR) AF: 0.00 AC: 0 AN: 33322

American (AMR) AF: 0.0000674 AC: 3 AN: 44486

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26056

East Asian (EAS) AF: 0.00167 AC: 66 AN: 39546

South Asian (SAS) AF: 0.0000349 AC: 3 AN: 85978

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53378

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5756

European-Non Finnish (NFE) AF: 0.00000540 AC: 6 AN: 1110274

Other (OTH) AF: 0.000183 AC: 11 AN: 60268

GnomAD4 genome AF: 0.0000855 AC: 13 AN: 151988 Hom.: 0 Cov.: 31 AF XY: 0.000135 AC XY: 10 AN XY: 74278

African (AFR) AF: 0.00 AC: 0 AN: 41450

American (AMR) AF: 0.0000656 AC: 1 AN: 15244

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00213 AC: 11 AN: 5170

South Asian (SAS) AF: 0.00 AC: 0 AN: 4816

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10540

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 292

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67990

Other (OTH) AF: 0.000475 AC: 1 AN: 2106

Alfa AF: 0.0000342 Hom.: 0

Bravo AF: 0.000155

ExAC AF: 0.000231 AC: 28

Asia WGS AF: 0.00115 AC: 4 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	Arrhythmogenic right ventricular dysplasia 13 (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.088
BayesDel_addAF	Benign	-0.51	T
BayesDel_noAF	Benign	-0.51
CADD	Benign	22
DANN	Uncertain	1.0
DEOGEN2	Benign	0.28	T
Eigen	Benign	-0.25
Eigen_PC	Benign	-0.25
FATHMM_MKL	Benign	0.74	D
LIST_S2	Benign	0.83	T
M_CAP	Benign	0.016	T
MetaRNN	Benign	0.013	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.0	N
PhyloP100		1.7
PrimateAI	Benign	0.27	T
PROVEAN	Uncertain	-2.6	D
REVEL	Benign	0.057
Sift	Uncertain	0.0070	D
Sift4G	Uncertain	0.010	D
Polyphen		0.0	B
Vest4		0.30
MVP		0.60
MPC		0.026
ClinPred		0.090	T
GERP RS		3.5
Varity_R		0.13
gMVP		0.23
Mutation Taster		=87/13	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: rs200182913; hg19: chr10-68280456; COSMIC: COSV104685578;