rs9971243

Variant names:

• chr10-66997087-T-C
• rs9971243
• NM_013266.4:c.1047+183230A>G

Variant summary

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

The NM_013266.4(CTNNA3):​c.1047+183230A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0939 in 152,188 control chromosomes in the GnomAD database, including 881 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 0.094 (881 hom., cov: 31)
• Consequence: CTNNA3 NM_013266.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.135
• 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]

LRRTM3 (HGNC:19410): (leucine rich repeat transmembrane neuronal 3) Involved in presynapse assembly. Acts upstream of or within positive regulation of amyloid-beta formation. Is active in glutamatergic synapse. [provided by Alliance of Genome Resources, Apr 2022]

ENSG00000302985 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.161 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.1047+183230A>G		intron	N/A	NP_037398.2	Q9UI47-1
	LRRTM3	NM_178011.5	MANE Select	c.1536+68635T>C		intron	N/A	NP_821079.3
	CTNNA3	NM_001127384.3		c.1047+183230A>G		intron	N/A	NP_001120856.1	Q9UI47-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CTNNA3	ENST00000433211.7	TSL:1 MANE Select	c.1047+183230A>G		intron	N/A	ENSP00000389714.1	Q9UI47-1
	LRRTM3	ENST00000361320.5	TSL:1 MANE Select	c.1536+68635T>C		intron	N/A	ENSP00000355187.3	Q86VH5-1
	CTNNA3	ENST00000682758.1		c.1047+183230A>G		intron	N/A	ENSP00000508047.1	Q9UI47-1

Frequencies

GnomAD3 genomes AF: 0.0938 AC: 14267 AN: 152070 Hom.: 877 Cov.: 31

Gnomad AFR AF: 0.164

Gnomad AMI AF: 0.0330

Gnomad AMR AF: 0.0784

Gnomad ASJ AF: 0.0714

Gnomad EAS AF: 0.000771

Gnomad SAS AF: 0.0221

Gnomad FIN AF: 0.0317

Gnomad MID AF: 0.0696

Gnomad NFE AF: 0.0782

Gnomad OTH AF: 0.0981

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

GnomAD4 genome AF: 0.0939 AC: 14287 AN: 152188 Hom.: 881 Cov.: 31 AF XY: 0.0886 AC XY: 6594 AN XY: 74416

African (AFR) AF: 0.165 AC: 6825 AN: 41488

American (AMR) AF: 0.0783 AC: 1197 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.0714 AC: 248 AN: 3472

East Asian (EAS) AF: 0.000773 AC: 4 AN: 5174

South Asian (SAS) AF: 0.0217 AC: 105 AN: 4832

European-Finnish (FIN) AF: 0.0317 AC: 336 AN: 10614

Middle Eastern (MID) AF: 0.0748 AC: 22 AN: 294

European-Non Finnish (NFE) AF: 0.0782 AC: 5316 AN: 68000

Other (OTH) AF: 0.0966 AC: 204 AN: 2112

Alfa AF: 0.0831 Hom.: 929

Bravo AF: 0.102

Asia WGS AF: 0.0210 AC: 77 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	2.0
DANN	Benign	0.40
PhyloP100		-0.14
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: rs9971243; hg19: chr10-68756845;