rs192093851

chr10-67219708-C-A

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_013266.4(CTNNA3):c.742G>T(p.Ala248Ser) variant causes a missense change. The variant allele was found at a frequency of 0.00106 in 1,614,092 control chromosomes in the GnomAD database, including 15 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0018 (4 hom., cov: 32)
  • Exomes 𝑓: 0.00098 (11 hom.)
• Consequence: CTNNA3 NM_013266.4 missense
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 4.40

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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.009857684).
• BP6: Variant 10-67219708-C-A is Benign according to our data. Variant chr10-67219708-C-A is described in ClinVar as [Benign]. Clinvar id is 415370.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High AC in GnomAd at 271 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CTNNA3	NM_013266.4	c.742G>T	p.Ala248Ser	missense_variant	6/18	ENST00000433211.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CTNNA3	ENST00000433211.7	c.742G>T	p.Ala248Ser	missense_variant	6/18	1	NM_013266.4	P1

Frequencies

GnomAD3 genomes AF: 0.00178 AC: 271 AN: 152128 Hom.: 4 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.0231

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000353

Gnomad OTH AF: 0.000959

GnomAD3 exomes AF: 0.00244 AC: 614 AN: 251392 Hom.: 6 AF XY: 0.00230 AC XY: 312 AN XY: 135870

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000653

Gnomad FIN exome AF: 0.0243

Gnomad NFE exome AF: 0.000677

Gnomad OTH exome AF: 0.00130

GnomAD4 exome AF: 0.000984 AC: 1439 AN: 1461846 Hom.: 11 Cov.: 31 AF XY: 0.000932 AC XY: 678 AN XY: 727228

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000116

Gnomad4 FIN exome AF: 0.0227

Gnomad4 NFE exome AF: 0.000144

Gnomad4 OTH exome AF: 0.000960

GnomAD4 genome AF: 0.00178 AC: 271 AN: 152246 Hom.: 4 Cov.: 32 AF XY: 0.00271 AC XY: 202 AN XY: 74436

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.0231

Gnomad4 NFE AF: 0.000353

Gnomad4 OTH AF: 0.000949

Alfa AF: 0.000260 Hom.: 0

Bravo AF: 0.0000831

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000233 AC: 2

ExAC AF: 0.00208 AC: 253

Asia WGS AF: 0.000289 AC: 1 AN: 3478

EpiCase AF: 0.000109

EpiControl AF: 0.000119

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Arrhythmogenic right ventricular dysplasia 13 Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jan 29, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Benign	-0.29	T
BayesDel_noAF	Benign	-0.24
Cadd	Uncertain	25
Dann	Uncertain	1.0
DEOGEN2	Benign	0.17	T;T
Eigen	Pathogenic	0.70
Eigen_PC	Pathogenic	0.70
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Benign	0.79	T;T
MetaRNN	Benign	0.0099	T;T
MetaSVM	Benign	-0.72	T
MutationAssessor	Benign	1.9	L;.
MutationTaster	Benign	1.0	D;D;D
PrimateAI	Uncertain	0.54	T
PROVEAN	Uncertain	-2.7	D;.
REVEL	Benign	0.23
Sift	Pathogenic	0.0	D;.
Sift4G	Benign	0.14	T;D
Polyphen		1.0	D;.
Vest4		0.49
MVP		0.56
MPC		0.099
ClinPred		0.086	T
GERP RS		5.5
Varity_R		0.61
gMVP		0.31

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: rs192093851; hg19: chr10-68979466;