12-41025179-A-C

Variant names:

• chr12-41025179-A-C
• rs150210369
• NM_001843.4:c.2553A>C

Variant summary

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

The NM_001843.4(CNTN1):​c.2553A>C​(p.Glu851Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. E851E) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: CNTN1 NM_001843.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.47
• 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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CNTN1	NM_001843.4	c.2553A>C	p.Glu851Asp	missense_variant	Exon 21 of 24	ENST00000551295.7	NP_001834.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CNTN1	ENST00000551295.7	c.2553A>C	p.Glu851Asp	missense_variant	Exon 21 of 24	1	NM_001843.4	ENSP00000447006.1
CNTN1	ENST00000347616.5	c.2553A>C	p.Glu851Asp	missense_variant	Exon 20 of 23	1		ENSP00000325660.3
CNTN1	ENST00000348761.2	c.2520A>C	p.Glu840Asp	missense_variant	Exon 19 of 22	1		ENSP00000261160.3
CNTN1	ENST00000550305.1	n.512A>C		non_coding_transcript_exon_variant	Exon 5 of 6	3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000399 AC: 1 AN: 250926 AF XY: 0.00000737

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000883

Gnomad OTH exome AF: 0.00

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ExAC AF: 0.00000824 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.39
BayesDel_addAF	Benign	-0.015	T
BayesDel_noAF	Benign	-0.26
CADD	Benign	21
DANN	Uncertain	1.0
DEOGEN2	Benign	0.39	T;T;.
Eigen	Benign	0.18
Eigen_PC	Benign	0.10
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Uncertain	0.97	.;D;D
M_CAP	Benign	0.027	D
MetaRNN	Uncertain	0.44	T;T;T
MetaSVM	Benign	-0.68	T
MutationAssessor	Uncertain	2.1	M;M;.
PhyloP100		2.5
PrimateAI	Uncertain	0.51	T
PROVEAN	Benign	-2.1	N;N;N
REVEL	Uncertain	0.33
Sift	Uncertain	0.0050	D;D;D
Sift4G	Uncertain	0.056	T;T;T
Polyphen		0.97	D;D;P
Vest4		0.36
MutPred		0.72		Gain of ubiquitination at K850 (P = 0.1797);Gain of ubiquitination at K850 (P = 0.1797);.;
MVP		0.56
MPC		0.97
ClinPred		0.84	D
GERP RS		1.2
Varity_R		0.64
gMVP		0.42
Mutation Taster		=44/56	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: rs150210369; hg19: chr12-41418981;