rs1555182848

Variant names:

• chr12-40929943-G-A
• rs1555182848
• NM_001843.4:c.644G>A

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_001843.4(CNTN1):​c.644G>A​(p.Ser215Asn) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000342 in 1,460,810 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. S215G) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000034 (0 hom.)
• Consequence: CNTN1 NM_001843.4 missense
• Clinical Significance: Uncertain significance criteria provided, multiple submitters, no conflicts U:2
• Conservation: PhyloP100: 7.73
• Publications: 0 publications found

Genes affected

CNTN1 (HGNC:2171): (contactin 1) 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. Multiple alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Dec 2011]

CNTN1 Gene-Disease associations (from GenCC):

• Compton-North congenital myopathy

  Inheritance: AR Classification: STRONG, MODERATE, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Orphanet, Ambry Genetics
• schizophrenia

  Inheritance: Unknown Classification: NO_KNOWN Submitted by: Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001843.4. 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
	CNTN1	NM_001843.4	MANE Select	c.644G>A	p.Ser215Asn	missense	Exon 7 of 24	NP_001834.2
	CNTN1	NM_175038.2		c.611G>A	p.Ser204Asn	missense	Exon 5 of 22	NP_778203.1	Q12860-2
	CNTN1	NM_001256063.2		c.644G>A	p.Ser215Asn	missense	Exon 7 of 16	NP_001242992.1	Q12860-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CNTN1	ENST00000551295.7	TSL:1 MANE Select	c.644G>A	p.Ser215Asn	missense	Exon 7 of 24	ENSP00000447006.1	Q12860-1
	CNTN1	ENST00000347616.5	TSL:1	c.644G>A	p.Ser215Asn	missense	Exon 6 of 23	ENSP00000325660.3	Q12860-1
	CNTN1	ENST00000348761.2	TSL:1	c.611G>A	p.Ser204Asn	missense	Exon 5 of 22	ENSP00000261160.3	Q12860-2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000342 AC: 5 AN: 1460810 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 726706

African (AFR) AF: 0.00 AC: 0 AN: 33418

American (AMR) AF: 0.00 AC: 0 AN: 44688

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26078

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39674

South Asian (SAS) AF: 0.00 AC: 0 AN: 86238

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53412

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5758

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111212

Other (OTH) AF: 0.0000663 AC: 4 AN: 60332

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	1	-	Compton-North congenital myopathy (1)
-	1	-	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.34
BayesDel_addAF	Benign	-0.041	T
BayesDel_noAF	Benign	-0.30
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Benign	0.29	T
Eigen	Uncertain	0.61
Eigen_PC	Uncertain	0.65
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Uncertain	0.91	D
M_CAP	Benign	0.013	T
MetaRNN	Uncertain	0.51	D
MetaSVM	Benign	-0.58	T
MutationAssessor	Benign	0.71	N
PhyloP100		7.7
PrimateAI	Pathogenic	0.80	T
PROVEAN	Benign	-0.070	N
REVEL	Benign	0.26
Sift	Benign	0.93	T
Sift4G	Benign	0.51	T
Polyphen		1.0	D
Vest4		0.48
MutPred		0.58		Loss of disorder (P = 0.0714)
MVP		0.61
MPC		0.99
ClinPred		0.98	D
GERP RS		5.4
Varity_R		0.54
gMVP		0.75
Mutation Taster		=11/89	disease causing

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

Other links and lift over

dbSNP: rs1555182848; hg19: chr12-41323745;