rs9332406

Variant names:

• chr10-66910441-C-A
• rs9332406
• NM_013266.4:c.1048-134917G>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_013266.4(CTNNA3):​c.1048-134917G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.31 in 152,146 control chromosomes in the GnomAD database, including 8,610 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.31 (8610 hom., cov: 32)
• Consequence: CTNNA3 NM_013266.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.397
• Publications: 2 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: Ambry Genetics, Labcorp Genetics (formerly Invitae)
• congenital heart disease

  Inheritance: Unknown Classification: NO_KNOWN Submitted by: ClinGen

LOC101928961 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.455 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CTNNA3	NM_013266.4	MANE Select	c.1048-134917G>T		intron	N/A	NP_037398.2	Q9UI47-1
	CTNNA3	NM_001127384.3		c.1048-134917G>T		intron	N/A	NP_001120856.1	Q9UI47-1
	LOC101928961	NR_111911.1		n.2770G>T		non_coding_transcript_exon	Exon 4 of 7

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CTNNA3	ENST00000433211.7	TSL:1 MANE Select	c.1048-134917G>T		intron	N/A	ENSP00000389714.1	Q9UI47-1
	CTNNA3	ENST00000682758.1		c.1048-134917G>T		intron	N/A	ENSP00000508047.1	Q9UI47-1
	CTNNA3	ENST00000684154.1		c.1048-134917G>T		intron	N/A	ENSP00000508371.1	Q9UI47-1

Frequencies

GnomAD3 genomes AF: 0.310 AC: 47109 AN: 152028 Hom.: 8601 Cov.: 32

Gnomad AFR AF: 0.113

Gnomad AMI AF: 0.352

Gnomad AMR AF: 0.411

Gnomad ASJ AF: 0.490

Gnomad EAS AF: 0.471

Gnomad SAS AF: 0.454

Gnomad FIN AF: 0.290

Gnomad MID AF: 0.358

Gnomad NFE AF: 0.377

Gnomad OTH AF: 0.346

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

GnomAD4 genome AF: 0.310 AC: 47122 AN: 152146 Hom.: 8610 Cov.: 32 AF XY: 0.311 AC XY: 23160 AN XY: 74370

African (AFR) AF: 0.113 AC: 4677 AN: 41514

American (AMR) AF: 0.410 AC: 6273 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.490 AC: 1699 AN: 3470

East Asian (EAS) AF: 0.471 AC: 2429 AN: 5160

South Asian (SAS) AF: 0.455 AC: 2195 AN: 4824

European-Finnish (FIN) AF: 0.290 AC: 3062 AN: 10576

Middle Eastern (MID) AF: 0.367 AC: 108 AN: 294

European-Non Finnish (NFE) AF: 0.377 AC: 25627 AN: 68000

Other (OTH) AF: 0.346 AC: 732 AN: 2114

Alfa AF: 0.328 Hom.: 1172

Bravo AF: 0.311

Asia WGS AF: 0.410 AC: 1425 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	5.5
DANN	Benign	0.42
PhyloP100		0.40
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: rs9332406; hg19: chr10-68670199;