NM_001843.4:c.1895G>A

Variant names:

• chr12-40980999-G-A
• rs199886411
• NM_001843.4:c.1895G>A

Variant summary

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

The NM_001843.4(CNTN1):​c.1895G>A​(p.Ser632Asn) variant causes a missense change. The variant allele was found at a frequency of 0.00000205 in 1,461,424 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: CNTN1 NM_001843.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.86
• 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), Ambry Genetics, Orphanet
• 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.1895G>A	p.Ser632Asn	missense	Exon 16 of 24	NP_001834.2
	CNTN1	NM_175038.2		c.1862G>A	p.Ser621Asn	missense	Exon 14 of 22	NP_778203.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CNTN1	ENST00000551295.7	TSL:1 MANE Select	c.1895G>A	p.Ser632Asn	missense	Exon 16 of 24	ENSP00000447006.1
	CNTN1	ENST00000347616.5	TSL:1	c.1895G>A	p.Ser632Asn	missense	Exon 15 of 23	ENSP00000325660.3
	CNTN1	ENST00000348761.2	TSL:1	c.1862G>A	p.Ser621Asn	missense	Exon 14 of 22	ENSP00000261160.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000205 AC: 3 AN: 1461424 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 727036

African (AFR) AF: 0.0000897 AC: 3 AN: 33462

American (AMR) AF: 0.00 AC: 0 AN: 44702

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26122

East Asian (EAS) AF: 0.00 AC: 0 AN: 39674

South Asian (SAS) AF: 0.00 AC: 0 AN: 86254

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53418

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5694

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111730

Other (OTH) AF: 0.00 AC: 0 AN: 60368

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions as Germline

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	Compton-North congenital myopathy (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.76
BayesDel_addAF	Benign	-0.081	T
BayesDel_noAF	Benign	-0.35
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.57	D
Eigen	Uncertain	0.66
Eigen_PC	Uncertain	0.63
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Uncertain	0.89	D
M_CAP	Benign	0.035	D
MetaRNN	Uncertain	0.52	D
MetaSVM	Uncertain	-0.28	T
MutationAssessor	Pathogenic	2.9	M
PhyloP100		4.9
PrimateAI	Uncertain	0.74	T
PROVEAN	Uncertain	-2.5	N
REVEL	Uncertain	0.29
Sift	Uncertain	0.0010	D
Sift4G	Uncertain	0.0040	D
Polyphen		0.83	P
Vest4		0.53
MutPred		0.64		Gain of catalytic residue at S632 (P = 0.0613)
MVP		0.62
MPC		0.39
ClinPred		0.97	D
GERP RS		4.7
Varity_R		0.36
gMVP		0.76
Mutation Taster		=85/15	polymorphism

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: rs199886411; hg19: chr12-41374801;