3-1227974-G-A

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_Moderate BP6_Moderate BP7 BS2

The NM_001289080.2(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 Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0047 (2 hom., cov: 32)
  • Exomes 𝑓: 0.0048 (27 hom.)
• Consequence: CNTN6 NM_001289080.2 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.64

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 -9 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 [Benign]. Clinvar id is 774840.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=1.63 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.339G>A	p.Lys113=	synonymous_variant	4/23	ENST00000446702.7

Ensembl

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

Frequencies

GnomAD3 genomes AF: 0.00467 AC: 710 AN: 152094 Hom.: 2 Cov.: 32

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.: 4 AF XY: 0.00284 AC XY: 383 AN XY: 134940

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.: 27 Cov.: 32 AF XY: 0.00464 AC XY: 3372 AN XY: 726742

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.: 2 Cov.: 32 AF XY: 0.00430 AC XY: 320 AN XY: 74432

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.: 0

Bravo AF: 0.00489

Asia WGS AF: 0.000289 AC: 1 AN: 3478

EpiCase AF: 0.00442

EpiControl AF: 0.00379

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Aug 22, 2018

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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

Other links and lift over

dbSNP: rs141581143; hg19: chr3-1269658;