rs6480244

Positions:

• chr10-66982638-A-C
• chr10-66982638-A-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_013266.4(CTNNA3):​c.1047+197679T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.617 in 151,978 control chromosomes in the GnomAD database, including 29,149 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 0.62 (29149 hom., cov: 32)
• Consequence: CTNNA3 NM_013266.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.434

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]

LOC101928961 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.691 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CTNNA3	NM_013266.4	c.1047+197679T>G		intron_variant		ENST00000433211.7
LRRTM3	NM_178011.5	c.1536+54186A>C		intron_variant		ENST00000361320.5
LOC101928961	NR_111911.1	n.1758T>G		non_coding_transcript_exon_variant	2/7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LRRTM3	ENST00000361320.5	c.1536+54186A>C		intron_variant		1	NM_178011.5	P1
CTNNA3	ENST00000433211.7	c.1047+197679T>G		intron_variant		1	NM_013266.4	P1

Frequencies

GnomAD3 genomes AF: 0.617 AC: 93747 AN: 151860 Hom.: 29108 Cov.: 32

Gnomad AFR AF: 0.604

Gnomad AMI AF: 0.602

Gnomad AMR AF: 0.702

Gnomad ASJ AF: 0.516

Gnomad EAS AF: 0.685

Gnomad SAS AF: 0.550

Gnomad FIN AF: 0.594

Gnomad MID AF: 0.535

Gnomad NFE AF: 0.615

Gnomad OTH AF: 0.620

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

GnomAD4 genome AF: 0.617 AC: 93842 AN: 151978 Hom.: 29149 Cov.: 32 AF XY: 0.617 AC XY: 45830 AN XY: 74262

Gnomad4 AFR AF: 0.605

Gnomad4 AMR AF: 0.702

Gnomad4 ASJ AF: 0.516

Gnomad4 EAS AF: 0.684

Gnomad4 SAS AF: 0.550

Gnomad4 FIN AF: 0.594

Gnomad4 NFE AF: 0.615

Gnomad4 OTH AF: 0.622

Alfa AF: 0.588 Hom.: 11476

Bravo AF: 0.628

Asia WGS AF: 0.621 AC: 2160 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	12
DANN	Benign	0.73

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: rs6480244; hg19: chr10-68742396;