10-67220095-G-A

Variant names:

• chr10-67220095-G-A
• rs9651325
• NM_013266.4:c.580-225C>T

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_013266.4(CTNNA3):​c.580-225C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.16 in 152,126 control chromosomes in the GnomAD database, including 2,549 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.16 (2549 hom., cov: 32)
• Consequence: CTNNA3 NM_013266.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.490
• Publications: 5 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

ACMG classification

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BP6: Variant 10-67220095-G-A is Benign according to our data. Variant chr10-67220095-G-A is described in ClinVar as Benign. ClinVar VariationId is 1295208.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.295 is higher than 0.05.

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.580-225C>T		intron	N/A	NP_037398.2
	CTNNA3	NM_001127384.3		c.580-225C>T		intron	N/A	NP_001120856.1
	CTNNA3	NM_001291133.2		c.616-225C>T		intron	N/A	NP_001278062.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CTNNA3	ENST00000433211.7	TSL:1 MANE Select	c.580-225C>T		intron	N/A	ENSP00000389714.1
	CTNNA3	ENST00000682758.1		c.580-225C>T		intron	N/A	ENSP00000508047.1
	CTNNA3	ENST00000684154.1		c.580-225C>T		intron	N/A	ENSP00000508371.1

Frequencies

GnomAD3 genomes AF: 0.160 AC: 24314 AN: 152008 Hom.: 2540 Cov.: 32

Gnomad AFR AF: 0.299

Gnomad AMI AF: 0.0439

Gnomad AMR AF: 0.103

Gnomad ASJ AF: 0.0580

Gnomad EAS AF: 0.137

Gnomad SAS AF: 0.0748

Gnomad FIN AF: 0.123

Gnomad MID AF: 0.0570

Gnomad NFE AF: 0.110

Gnomad OTH AF: 0.134

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.160 AC: 24349 AN: 152126 Hom.: 2549 Cov.: 32 AF XY: 0.159 AC XY: 11862 AN XY: 74380

African (AFR) AF: 0.299 AC: 12415 AN: 41468

American (AMR) AF: 0.103 AC: 1569 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.0580 AC: 201 AN: 3468

East Asian (EAS) AF: 0.137 AC: 709 AN: 5174

South Asian (SAS) AF: 0.0747 AC: 360 AN: 4822

European-Finnish (FIN) AF: 0.123 AC: 1304 AN: 10594

Middle Eastern (MID) AF: 0.0578 AC: 17 AN: 294

European-Non Finnish (NFE) AF: 0.110 AC: 7452 AN: 67996

Other (OTH) AF: 0.133 AC: 282 AN: 2114

Alfa AF: 0.115 Hom.: 1515

Bravo AF: 0.164

Asia WGS AF: 0.104 AC: 363 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Sep 11, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	5.8
DANN	Benign	0.23
PhyloP100		0.49
Mutation Taster		=100/0	polymorphism (auto)

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: rs9651325; hg19: chr10-68979853;