9-39086816-T-G

Variant names:

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2BP4

The NM_033655.5(CNTNAP3):c.3254A>C(p.His1085Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000807 in 1,610,098 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 29)

Exomes 𝑓: 0.0000082 ( 0 hom. )

Consequence

CNTNAP3
NM_033655.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.45

Publications

0 publications found

Variant links:

Genes affected

CNTNAP3 (HGNC:13834): (contactin associated protein family member 3) The protein encoded by this gene belongs to the NCP family of cell-recognition molecules. This family represents a distinct subgroup of the neurexins. NCP proteins mediate neuron-glial interactions in vertebrates and glial-glial contact in invertebrates. The protein encoded by this gene may play a role in cell recognition within the nervous system. Alternatively spliced transcript variants encoding different isoforms have been described but their biological nature has not been determined. [provided by RefSeq, Jul 2008]

CNTNAP3 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.3427843).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CNTNAP3	NM_033655.5 link	c.3254A>C	p.His1085Pro	missense_variant	Exon 20 of 24	ENST00000297668.11	NP_387504.2	Q9BZ76-1
CNTNAP3	NM_001393379.1 link	c.3011A>C	p.His1004Pro	missense_variant	Exon 19 of 23		NP_001380308.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
CNTNAP3	ENST00000297668.11 link	c.3254A>C	p.His1085Pro	missense_variant	Exon 20 of 24	1	NM_033655.5	ENSP00000297668.6	Q9BZ76-1
CNTNAP3	ENST00000377656.6 link	c.3011A>C	p.His1004Pro	missense_variant	Exon 19 of 23	1		ENSP00000366884.2	A6NC89
CNTNAP3	ENST00000358144.6 link	c.2990A>C	p.His997Pro	missense_variant	Exon 18 of 18	5		ENSP00000350863.2	B1AMA2
CNTNAP3	ENST00000493965.5 link	n.85A>C		non_coding_transcript_exon_variant	Exon 2 of 5	5

Frequencies

GnomAD3 genomes

AF:

0.00000662

AC:

AN:

151072

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.00000822

AC:

AN:

1459026

Hom.:

Cov.:

AF XY:

0.00000964

AC XY:

AN XY:

725818

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33384

American (AMR)

AF:

0.00

AC:

AN:

44690

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26116

East Asian (EAS)

AF:

0.00

AC:

AN:

39652

South Asian (SAS)

AF:

0.00

AC:

AN:

86074

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53412

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4132

European-Non Finnish (NFE)

AF:

0.0000108

AC:

AN:

1111402

Other (OTH)

AF:

0.00

AC:

AN:

60164

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.488

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.00000662

AC:

AN:

151072

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

73712

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41032

American (AMR)

AF:

0.00

AC:

AN:

15162

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3466

East Asian (EAS)

AF:

0.00

AC:

AN:

5156

South Asian (SAS)

AF:

0.00

AC:

AN:

4742

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10378

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.0000147

AC:

AN:

67842

Other (OTH)

AF:

0.00

AC:

AN:

2066

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Mar 28, 2024

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The c.3254A>C (p.H1085P) alteration is located in exon 20 (coding exon 20) of the CNTNAP3 gene. This alteration results from a A to C substitution at nucleotide position 3254, causing the histidine (H) at amino acid position 1085 to be replaced by a proline (P). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.19

BayesDel_addAF

Uncertain

0.14

BayesDel_noAF

Uncertain

-0.030

CADD

Benign

(source)

DANN

Benign

0.91

DEOGEN2

Benign

0.35

T;.;.

Eigen

Benign

-0.080

Eigen_PC

Benign

-0.19

FATHMM_MKL

Benign

0.57

LIST_S2

Benign

0.84

T;D;D

M_CAP

Benign

0.053

MetaRNN

Benign

0.34

T;T;T

MetaSVM

Benign

-0.62

MutationAssessor

Uncertain

2.6

M;.;.

PhyloP100

2.4

PrimateAI

Uncertain

0.65

PROVEAN

Uncertain

-3.6

D;D;D

REVEL

Uncertain

0.52

Sift

Benign

0.21

T;T;T

Sift4G

Benign

0.21

T;T;T

Polyphen

0.91

P;D;.

Vest4

0.50

MutPred

0.53

Loss of sheet (P = 0.0315);.;.;

MVP

0.75

ClinPred

0.58

GERP RS

2.7

Varity_R

0.46

gMVP

0.45

Mutation Taster

=88/12

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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.

9-39086816-T-G

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over