3-74295205-T-G

Variant names:

• chr3-74295205-T-G
• rs10490832
• NM_020872.3:c.2433A>C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6 BP7 BA1

The NM_020872.3(CNTN3):​c.2433A>C​(p.Ala811Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.147 in 1,610,212 control chromosomes in the GnomAD database, including 18,913 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.11 (1249 hom., cov: 32)
  • Exomes 𝑓: 0.15 (17664 hom.)
• Consequence: CNTN3 NM_020872.3 synonymous
• Clinical Significance: Benign no assertion criteria provided B:1
• Conservation: PhyloP100: -0.475

Genes affected

CNTN3 (HGNC:2173): (contactin 3) Predicted to be involved in cell adhesion and nervous system development. Predicted to be located in extracellular region and plasma membrane. Predicted to be active in neuron projection. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BP6: Variant 3-74295205-T-G is Benign according to our data. Variant chr3-74295205-T-G is described in ClinVar as [Benign]. Clinvar id is 3055362.Status of the report is no_assertion_criteria_provided, 0 stars.
• BP7: Synonymous conserved (PhyloP=-0.475 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.161 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CNTN3	NM_020872.3	c.2433A>C	p.Ala811Ala	synonymous_variant	Exon 19 of 23	ENST00000263665.7	NP_065923.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CNTN3	ENST00000263665.7	c.2433A>C	p.Ala811Ala	synonymous_variant	Exon 19 of 23	1	NM_020872.3	ENSP00000263665.6

Frequencies

GnomAD3 genomes AF: 0.111 AC: 16941 AN: 152170 Hom.: 1251 Cov.: 32

Gnomad AFR AF: 0.0262

Gnomad AMI AF: 0.104

Gnomad AMR AF: 0.0888

Gnomad ASJ AF: 0.176

Gnomad EAS AF: 0.0289

Gnomad SAS AF: 0.171

Gnomad FIN AF: 0.144

Gnomad MID AF: 0.165

Gnomad NFE AF: 0.161

Gnomad OTH AF: 0.120

GnomAD3 exomes AF: 0.128 AC: 32187 AN: 250704 Hom.: 2485 AF XY: 0.135 AC XY: 18254 AN XY: 135474

Gnomad AFR exome AF: 0.0244

Gnomad AMR exome AF: 0.0694

Gnomad ASJ exome AF: 0.181

Gnomad EAS exome AF: 0.0305

Gnomad SAS exome AF: 0.174

Gnomad FIN exome AF: 0.141

Gnomad NFE exome AF: 0.157

Gnomad OTH exome AF: 0.139

GnomAD4 exome AF: 0.150 AC: 219182 AN: 1457924 Hom.: 17664 Cov.: 29 AF XY: 0.152 AC XY: 110228 AN XY: 725398

Gnomad4 AFR exome AF: 0.0233

Gnomad4 AMR exome AF: 0.0729

Gnomad4 ASJ exome AF: 0.182

Gnomad4 EAS exome AF: 0.0271

Gnomad4 SAS exome AF: 0.178

Gnomad4 FIN exome AF: 0.138

Gnomad4 NFE exome AF: 0.160

Gnomad4 OTH exome AF: 0.143

GnomAD4 genome AF: 0.111 AC: 16941 AN: 152288 Hom.: 1249 Cov.: 32 AF XY: 0.110 AC XY: 8204 AN XY: 74464

Gnomad4 AFR AF: 0.0261

Gnomad4 AMR AF: 0.0886

Gnomad4 ASJ AF: 0.176

Gnomad4 EAS AF: 0.0293

Gnomad4 SAS AF: 0.170

Gnomad4 FIN AF: 0.144

Gnomad4 NFE AF: 0.161

Gnomad4 OTH AF: 0.120

Alfa AF: 0.149 Hom.: 4529

Bravo AF: 0.102

Asia WGS AF: 0.117 AC: 407 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

Submissions by phenotype

CNTN3-related disorder Benign:1

Oct 30, 2019

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	7.2
DANN	Benign	0.53

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: rs10490832; hg19: chr3-74344356; COSMIC: COSV55188997;