NM_001843.4:c.2002G>C

Variant names:

• chr12-40993158-G-C
• NM_001843.4:c.2002G>C

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_001843.4(CNTN1):​c.2002G>C​(p.Ala668Pro) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,338 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: CNTN1 NM_001843.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 9.36

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.904

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CNTN1	NM_001843.4	c.2002G>C	p.Ala668Pro	missense_variant	Exon 17 of 24	ENST00000551295.7	NP_001834.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CNTN1	ENST00000551295.7	c.2002G>C	p.Ala668Pro	missense_variant	Exon 17 of 24	1	NM_001843.4	ENSP00000447006.1
CNTN1	ENST00000347616.5	c.2002G>C	p.Ala668Pro	missense_variant	Exon 16 of 23	1		ENSP00000325660.3
CNTN1	ENST00000348761.2	c.1969G>C	p.Ala657Pro	missense_variant	Exon 15 of 22	1		ENSP00000261160.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461338 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 727024

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 9.00e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.92
BayesDel_addAF	Uncertain	0.13	D
BayesDel_noAF	Uncertain	-0.060
CADD	Pathogenic	27
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.46	T;T;.
Eigen	Pathogenic	0.79
Eigen_PC	Pathogenic	0.79
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.96	.;D;D
M_CAP	Benign	0.037	D
MetaRNN	Pathogenic	0.90	D;D;D
MetaSVM	Benign	-0.46	T
MutationAssessor	Benign	1.5	L;L;.
PrimateAI	Uncertain	0.59	T
PROVEAN	Benign	-2.2	N;N;N
REVEL	Uncertain	0.38
Sift	Uncertain	0.0040	D;D;D
Sift4G	Uncertain	0.013	D;D;D
Polyphen		0.99	D;D;D
Vest4		0.69
MutPred		0.79		Loss of sheet (P = 0.0817);Loss of sheet (P = 0.0817);.;
MVP		0.28
MPC		1.1
ClinPred		0.94	D
GERP RS		5.2
Varity_R		0.80
gMVP		0.92

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr12-41386960;