3-1295687-T-C

Variant summary

Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP4_Strong BP6_Very_Strong BP7 BS2

The NM_001289080.2(CNTN6):c.541T>C(p.Leu181=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0101 in 1,614,044 control chromosomes in the GnomAD database, including 112 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0064 (2 hom., cov: 33)
  • Exomes 𝑓: 0.011 (110 hom.)
• Consequence: CNTN6 NM_001289080.2 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.187

Genes affected

CNTN6 (HGNC:2176): (contactin 6) The protein encoded by this gene is a member of the immunoglobulin superfamily. It is a glycosylphosphatidylinositol (GPI)-anchored neuronal membrane protein that functions as a cell adhesion molecule. It may play a role in the formation of axon connections in the developing nervous system. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jan 2014]

ACMG classification

Verdict is Benign. Variant got -17 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.56).
• BP6: Variant 3-1295687-T-C is Benign according to our data. Variant chr3-1295687-T-C is described in ClinVar as [Benign]. Clinvar id is 773437.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.187 with no splicing effect.
• BS2: High Homozygotes in GnomAd at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CNTN6	NM_001289080.2	c.541T>C	p.Leu181=	synonymous_variant	6/23	ENST00000446702.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CNTN6	ENST00000446702.7	c.541T>C	p.Leu181=	synonymous_variant	6/23	1	NM_001289080.2	P1
CNTN6	ENST00000350110.2	c.541T>C	p.Leu181=	synonymous_variant	6/23	1		P1
CNTN6	ENST00000394261.2	c.*519T>C		3_prime_UTR_variant, NMD_transcript_variant	7/8	1
CNTN6	ENST00000397479.6	c.*679T>C		3_prime_UTR_variant, NMD_transcript_variant	5/22	2

Frequencies

GnomAD3 genomes AF: 0.00646 AC: 983 AN: 152224 Hom.: 2 Cov.: 33

Gnomad AFR AF: 0.00207

Gnomad AMI AF: 0.00110

Gnomad AMR AF: 0.00406

Gnomad ASJ AF: 0.00605

Gnomad EAS AF: 0.000385

Gnomad SAS AF: 0.0108

Gnomad FIN AF: 0.00122

Gnomad MID AF: 0.0190

Gnomad NFE AF: 0.0106

Gnomad OTH AF: 0.00907

GnomAD3 exomes AF: 0.00769 AC: 1923 AN: 250166 Hom.: 9 AF XY: 0.00858 AC XY: 1160 AN XY: 135240

Gnomad AFR exome AF: 0.00173

Gnomad AMR exome AF: 0.00498

Gnomad ASJ exome AF: 0.00547

Gnomad EAS exome AF: 0.0000544

Gnomad SAS exome AF: 0.0113

Gnomad FIN exome AF: 0.00222

Gnomad NFE exome AF: 0.0108

Gnomad OTH exome AF: 0.00966

GnomAD4 exome AF: 0.0105 AC: 15350 AN: 1461702 Hom.: 110 Cov.: 31 AF XY: 0.0106 AC XY: 7719 AN XY: 727148

Gnomad4 AFR exome AF: 0.00212

Gnomad4 AMR exome AF: 0.00483

Gnomad4 ASJ exome AF: 0.00494

Gnomad4 EAS exome AF: 0.0000252

Gnomad4 SAS exome AF: 0.0125

Gnomad4 FIN exome AF: 0.00279

Gnomad4 NFE exome AF: 0.0118

Gnomad4 OTH exome AF: 0.00896

GnomAD4 genome AF: 0.00645 AC: 982 AN: 152342 Hom.: 2 Cov.: 33 AF XY: 0.00604 AC XY: 450 AN XY: 74496

Gnomad4 AFR AF: 0.00207

Gnomad4 AMR AF: 0.00405

Gnomad4 ASJ AF: 0.00605

Gnomad4 EAS AF: 0.000386

Gnomad4 SAS AF: 0.0108

Gnomad4 FIN AF: 0.00122

Gnomad4 NFE AF: 0.0106

Gnomad4 OTH AF: 0.00898

Alfa AF: 0.00886 Hom.: 3

Bravo AF: 0.00631

Asia WGS AF: 0.00664 AC: 23 AN: 3478

EpiCase AF: 0.0113

EpiControl AF: 0.0108

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	Invitae	Dec 31, 2019	- -
Benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Dec 01, 2023	CNTN6: BP4, BP7, BS1, BS2 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.56
Cadd	Benign	3.1
Dann	Benign	0.72

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: rs150338565; hg19: chr3-1337371; COSMIC: COSV63183510;