10-65919290-A-G

Position:

• chr10-65919290-A-G

Variant summary

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

The NM_013266.4(CTNNA3):​c.*1040T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.275 in 152,098 control chromosomes in the GnomAD database, including 6,829 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 0.27 (6829 hom., cov: 32)
  • Failed GnomAD Quality Control
• Consequence: CTNNA3 NM_013266.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.794

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.78).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.357 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CTNNA3	NM_013266.4	c.*1040T>C		3_prime_UTR_variant	18/18	ENST00000433211.7	NP_037398.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CTNNA3	ENST00000433211	c.*1040T>C		3_prime_UTR_variant	18/18	1	NM_013266.4	ENSP00000389714.1

Frequencies

GnomAD3 genomes AF: 0.275 AC: 41765 AN: 151980 Hom.: 6830 Cov.: 32

Gnomad AFR AF: 0.0941

Gnomad AMI AF: 0.236

Gnomad AMR AF: 0.289

Gnomad ASJ AF: 0.243

Gnomad EAS AF: 0.371

Gnomad SAS AF: 0.339

Gnomad FIN AF: 0.432

Gnomad MID AF: 0.288

Gnomad NFE AF: 0.347

Gnomad OTH AF: 0.290

GnomAD4 exome Data not reliable, filtered out with message: AC0 AC: 0 AN: 0 Hom.: 0 Cov.: 0 AC XY: 0 AN XY: 0

GnomAD4 genome AF: 0.275 AC: 41767 AN: 152098 Hom.: 6829 Cov.: 32 AF XY: 0.280 AC XY: 20776 AN XY: 74324

Gnomad4 AFR AF: 0.0940

Gnomad4 AMR AF: 0.288

Gnomad4 ASJ AF: 0.243

Gnomad4 EAS AF: 0.371

Gnomad4 SAS AF: 0.339

Gnomad4 FIN AF: 0.432

Gnomad4 NFE AF: 0.347

Gnomad4 OTH AF: 0.290

Alfa AF: 0.325 Hom.: 10904

Bravo AF: 0.254

Asia WGS AF: 0.366 AC: 1270 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	3.4
DANN	Benign	0.70

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: rs1786929; hg19: chr10-67679048;