dbSNP rs774602662: CNTN4:p.Glu765Ala (chr3-3040167-A-C) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

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

The NM_175607.3(CNTN4):c.2294A>C(p.Glu765Ala) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,852 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. E765D) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 34)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

CNTN4
NM_175607.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 9.10

Publications

0 publications found

Variant links:

Genes affected

CNTN4 (HGNC:2174): (contactin 4) This gene encodes a member of the contactin family of immunoglobulins. Contactins are axon-associated cell adhesion molecules that function in neuronal network formation and plasticity. The encoded protein is a glycosylphosphatidylinositol-anchored neuronal membrane protein that may play a role in the formation of axon connections in the developing nervous system. Deletion or mutation of this gene may play a role in 3p deletion syndrome and autism spectrum disorders. Alternative splicing results in multiple transcript variants. [provided by RefSeq, May 2011]

CNTN4 links:

CNTN4-AS1 (HGNC:39985): (CNTN4 antisense RNA 1)

CNTN4-AS1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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_175607.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CNTN4	NM_175607.3	MANE Select	c.2294A>C	p.Glu765Ala	missense	Exon 20 of 25	NP_783200.1	Q8IWV2-1
CNTN4	NM_001206955.2		c.2294A>C	p.Glu765Ala	missense	Exon 19 of 24	NP_001193884.1	Q8IWV2-1
CNTN4	NM_001350095.2		c.2294A>C	p.Glu765Ala	missense	Exon 20 of 25	NP_001337024.1	Q8IWV2-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CNTN4	ENST00000418658.6	TSL:5 MANE Select	c.2294A>C	p.Glu765Ala	missense	Exon 20 of 25	ENSP00000396010.1	Q8IWV2-1
CNTN4	ENST00000397459.6	TSL:1	c.1310A>C	p.Glu437Ala	missense	Exon 11 of 16	ENSP00000380600.2	Q8IWV2-4
CNTN4	ENST00000484686.1	TSL:1	n.544A>C		non_coding_transcript_exon	Exon 1 of 6

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461852

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

727228

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33480

American (AMR)

AF:

0.00

AC:

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26136

East Asian (EAS)

AF:

0.00

AC:

AN:

39700

South Asian (SAS)

AF:

0.0000116

AC:

AN:

86254

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53420

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1111974

Other (OTH)

AF:

0.00

AC:

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.625

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.24

BayesDel_addAF

Uncertain

0.13

BayesDel_noAF

Uncertain

-0.050

CADD

Pathogenic

(source)

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.57

Eigen

Uncertain

0.66

Eigen_PC

Uncertain

0.66

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Pathogenic

0.99

M_CAP

Benign

0.046

MetaRNN

Uncertain

0.72

MetaSVM

Benign

-0.54

MutationAssessor

Uncertain

2.5

PhyloP100

9.1

PrimateAI

Uncertain

0.67

PROVEAN

Uncertain

-4.3

REVEL

Uncertain

0.39

Sift

Uncertain

0.0020

Sift4G

Uncertain

0.015

Polyphen

0.95

Vest4

0.70

MutPred

0.45

Gain of glycosylation at S766 (P = 0.0297)

MVP

0.67

MPC

0.23

ClinPred

0.99

GERP RS

5.0

Varity_R

0.62

gMVP

0.46

Mutation Taster

=57/43

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over