Variant 3-1227974-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_ModerateBP6_Very_StrongBP7BS2

The ENST00000446702.7(CNTN6):c.339G>A(p.Lys113=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00481 in 1,613,192 control chromosomes in the GnomAD database, including 29 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0047 ( 2 hom., cov: 32)

Exomes 𝑓: 0.0048 ( 27 hom. )

Consequence

CNTN6
ENST00000446702.7 synonymous

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 1.64

Variant links:

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]

CNTN6 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -15 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.37).

BP6

Variant 3-1227974-G-A is Benign according to our data. Variant chr3-1227974-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 774840.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=1.63 with no splicing effect.

BS2

High Homozygotes in GnomAd4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CNTN6	NM_001289080.2 linkuse as main transcript	c.339G>A	p.Lys113=	synonymous_variant	4/23	ENST00000446702.7	NP_001276009.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris
CNTN6	ENST00000446702.7 linkuse as main transcript	c.339G>A	p.Lys113=	synonymous_variant	4/23	1	NM_001289080.2	ENSP00000407822	P1
CNTN6	ENST00000350110.2 linkuse as main transcript	c.339G>A	p.Lys113=	synonymous_variant	4/23	1		ENSP00000341882	P1
CNTN6	ENST00000394261.2 linkuse as main transcript	c.*317G>A		3_prime_UTR_variant, NMD_transcript_variant	5/8	1		ENSP00000377804
CNTN6	ENST00000397479.6 linkuse as main transcript	c.*477G>A		3_prime_UTR_variant, NMD_transcript_variant	3/22	2		ENSP00000380616

Frequencies

GnomAD3 genomes

AF:

0.00467

AC:

710

AN:

152094

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00611

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00380

Gnomad ASJ

AF:

0.000288

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000188

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00569

Gnomad OTH

AF:

0.00430

GnomAD3 exomes

AF:

0.00305

AC:

763

AN:

249770

Hom.:

AF XY:

0.00284

AC XY:

383

AN XY:

134940

show subpopulations

Gnomad AFR exome

AF:

0.00647

Gnomad AMR exome

AF:

0.00187

Gnomad ASJ exome

AF:

0.000700

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000662

Gnomad FIN exome

AF:

0.000139

Gnomad NFE exome

AF:

0.00502

Gnomad OTH exome

AF:

0.00231

GnomAD4 exome

AF:

0.00483

AC:

7056

AN:

1460980

Hom.:

Cov.:

AF XY:

0.00464

AC XY:

3372

AN XY:

726742

show subpopulations

Gnomad4 AFR exome

AF:

0.00756

Gnomad4 AMR exome

AF:

0.00177

Gnomad4 ASJ exome

AF:

0.000728

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000814

Gnomad4 FIN exome

AF:

0.000243

Gnomad4 NFE exome

AF:

0.00580

Gnomad4 OTH exome

AF:

0.00378

GnomAD4 genome

AF:

0.00466

AC:

710

AN:

152212

Hom.:

Cov.:

AF XY:

0.00430

AC XY:

320

AN XY:

74432

show subpopulations

Gnomad4 AFR

AF:

0.00609

Gnomad4 AMR

AF:

0.00379

Gnomad4 ASJ

AF:

0.000288

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.000188

Gnomad4 NFE

AF:

0.00569

Gnomad4 OTH

AF:

0.00425

Alfa

AF:

0.00487

Hom.:

Bravo

AF:

0.00489

Asia WGS

AF:

0.000289

AC:

AN:

3478

EpiCase

AF:

0.00442

EpiControl

AF:

0.00379

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Jul 01, 2024	CNTN6: BP4, BP7, BS2 -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Aug 22, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.37

CADD

Benign

6.4

DANN

Benign

0.61

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over