ENST00000425765.1:n.864C>T

Variant names:

• chr10-67751147-C-T
• rs10997795
• ENST00000425765.1:n.864C>T

Variant summary

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

The ENST00000425765.1(AKR1B10P1):​n.864C>T variant causes a non coding transcript exon change. The variant allele was found at a frequency of 0.119 in 1,306,556 control chromosomes in the GnomAD database, including 14,928 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 0.18 (3437 hom., cov: 32)
  • Exomes 𝑓: 0.11 (11491 hom.)
• Consequence: AKR1B10P1 ENST00000425765.1 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.95
• Publications: 3 publications found

Genes affected

AKR1B10P1 (HGNC:45062): (aldo-keto reductase family 1 member B10 pseudogene 1)

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: Labcorp Genetics (formerly Invitae), Ambry Genetics
• congenital heart disease

  Inheritance: Unknown Classification: NO_KNOWN Submitted by: ClinGen

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 = 0.421 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AKR1B10P1		n.67751147C>T		intragenic_variant
CTNNA3	XM_047425124.1	c.-47+12287G>A		intron_variant	Intron 1 of 18		XP_047281080.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AKR1B10P1	ENST00000425765.1	n.864C>T		non_coding_transcript_exon_variant	Exon 1 of 1	6
CTNNA3	ENST00000684154.1	c.-2+12287G>A		intron_variant	Intron 1 of 17			ENSP00000508371.1

Frequencies

GnomAD3 genomes AF: 0.176 AC: 26754 AN: 152068 Hom.: 3422 Cov.: 32

Gnomad AFR AF: 0.333

Gnomad AMI AF: 0.120

Gnomad AMR AF: 0.140

Gnomad ASJ AF: 0.0931

Gnomad EAS AF: 0.436

Gnomad SAS AF: 0.204

Gnomad FIN AF: 0.153

Gnomad MID AF: 0.166

Gnomad NFE AF: 0.0752

Gnomad OTH AF: 0.168

GnomAD4 exome AF: 0.112 AC: 129231 AN: 1154368 Hom.: 11491 Cov.: 23 AF XY: 0.114 AC XY: 66891 AN XY: 587952

African (AFR) AF: 0.346 AC: 9550 AN: 27600

American (AMR) AF: 0.148 AC: 6502 AN: 44068

Ashkenazi Jewish (ASJ) AF: 0.0858 AC: 2074 AN: 24160

East Asian (EAS) AF: 0.445 AC: 16955 AN: 38144

South Asian (SAS) AF: 0.201 AC: 16067 AN: 80032

European-Finnish (FIN) AF: 0.146 AC: 7714 AN: 52676

Middle Eastern (MID) AF: 0.171 AC: 881 AN: 5162

European-Non Finnish (NFE) AF: 0.0755 AC: 62832 AN: 832538

Other (OTH) AF: 0.133 AC: 6656 AN: 49988

GnomAD4 genome AF: 0.176 AC: 26815 AN: 152188 Hom.: 3437 Cov.: 32 AF XY: 0.181 AC XY: 13466 AN XY: 74404

African (AFR) AF: 0.334 AC: 13843 AN: 41488

American (AMR) AF: 0.141 AC: 2153 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.0931 AC: 323 AN: 3468

East Asian (EAS) AF: 0.436 AC: 2256 AN: 5172

South Asian (SAS) AF: 0.205 AC: 991 AN: 4830

European-Finnish (FIN) AF: 0.153 AC: 1626 AN: 10594

Middle Eastern (MID) AF: 0.156 AC: 46 AN: 294

European-Non Finnish (NFE) AF: 0.0752 AC: 5114 AN: 68024

Other (OTH) AF: 0.167 AC: 354 AN: 2116

Alfa AF: 0.126 Hom.: 315

Bravo AF: 0.187

Asia WGS AF: 0.310 AC: 1075 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	3.7
DANN	Benign	0.64
PhyloP100		3.9

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs10997795; hg19: chr10-69510905;