rs9651325

Positions:

• chr10-67220095-G-A
• chr10-67220095-G-C

Variant summary

Our verdict is Benign. Variant got -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

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]

ACMG classification

Verdict is Benign. Variant got -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 id 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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CTNNA3	NM_013266.4	c.580-225C>T		intron_variant		ENST00000433211.7	NP_037398.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CTNNA3	ENST00000433211.7	c.580-225C>T		intron_variant		1	NM_013266.4	ENSP00000389714	P1

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

Gnomad4 AFR AF: 0.299

Gnomad4 AMR AF: 0.103

Gnomad4 ASJ AF: 0.0580

Gnomad4 EAS AF: 0.137

Gnomad4 SAS AF: 0.0747

Gnomad4 FIN AF: 0.123

Gnomad4 NFE AF: 0.110

Gnomad4 OTH AF: 0.133

Alfa AF: 0.104 Hom.: 853

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

Benign, criteria provided, single submitter

clinical testing

GeneDx

Sep 11, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	5.8
DANN	Benign	0.23

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

LitVar

Other links and lift over

dbSNP: rs9651325; hg19: chr10-68979853;