rs141581143

Variant names:

• chr3-1227974-G-A
• rs141581143
• NM_001289080.2:c.339G>A

Your query was ambiguous. Multiple possible variants found:

• chr3-1227974-G-A
• chr3-1227974-G-T

Variant summary

Our verdict is Benign. The variant received -15 ACMG points: 0P and 15B. BP4_Moderate BP6_Very_Strong BP7 BS2

The NM_001289080.2(CNTN6):​c.339G>A​(p.Lys113Lys) 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 NM_001289080.2 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 1.64
• Publications: 2 publications found

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 Gene-Disease associations (from GenCC):

• Tourette syndrome

  Inheritance: Unknown Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae)
• complex neurodevelopmental disorder

  Inheritance: AD Classification: NO_KNOWN Submitted by: ClinGen

ACMG classification

Our verdict: Benign. The variant received -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 Benign/Likely_benign. ClinVar VariationId 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 AC in GnomAd4 at 710 Unknown,AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001289080.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CNTN6	NM_001289080.2	MANE Select	c.339G>A	p.Lys113Lys	synonymous	Exon 4 of 23	NP_001276009.1	Q9UQ52
	CNTN6	NM_001349350.2		c.339G>A	p.Lys113Lys	synonymous	Exon 6 of 25	NP_001336279.1	Q9UQ52
	CNTN6	NM_001349351.2		c.339G>A	p.Lys113Lys	synonymous	Exon 6 of 25	NP_001336280.1	Q9UQ52

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CNTN6	ENST00000446702.7	TSL:1 MANE Select	c.339G>A	p.Lys113Lys	synonymous	Exon 4 of 23	ENSP00000407822.2	Q9UQ52
	CNTN6	ENST00000350110.2	TSL:1	c.339G>A	p.Lys113Lys	synonymous	Exon 4 of 23	ENSP00000341882.2	Q9UQ52
	CNTN6	ENST00000394261.2	TSL:1	n.*317G>A		non_coding_transcript_exon	Exon 5 of 8	ENSP00000377804.2	F8WDQ0

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

GnomAD2 exomes AF: 0.00305 AC: 763 AN: 249770 AF XY: 0.00284

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 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

African (AFR) AF: 0.00756 AC: 253 AN: 33448

American (AMR) AF: 0.00177 AC: 79 AN: 44538

Ashkenazi Jewish (ASJ) AF: 0.000728 AC: 19 AN: 26092

East Asian (EAS) AF: 0.00 AC: 0 AN: 39686

South Asian (SAS) AF: 0.0000814 AC: 7 AN: 85992

European-Finnish (FIN) AF: 0.000243 AC: 13 AN: 53414

Middle Eastern (MID) AF: 0.00139 AC: 8 AN: 5766

European-Non Finnish (NFE) AF: 0.00580 AC: 6449 AN: 1111674

Other (OTH) AF: 0.00378 AC: 228 AN: 60370

GnomAD4 genome AF: 0.00466 AC: 710 AN: 152212 Hom.: 2 Cov.: 32 AF XY: 0.00430 AC XY: 320 AN XY: 74432

African (AFR) AF: 0.00609 AC: 253 AN: 41532

American (AMR) AF: 0.00379 AC: 58 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.000288 AC: 1 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5168

South Asian (SAS) AF: 0.00 AC: 0 AN: 4812

European-Finnish (FIN) AF: 0.000188 AC: 2 AN: 10612

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 292

European-Non Finnish (NFE) AF: 0.00569 AC: 387 AN: 68014

Other (OTH) AF: 0.00425 AC: 9 AN: 2116

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

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not provided (3)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.37
CADD	Benign	6.4
DANN	Benign	0.61
PhyloP100		1.6
Mutation Taster		=95/5	polymorphism

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

Other links and lift over

dbSNP: rs141581143; hg19: chr3-1269658; COSMIC: COSV108181140;