Genetic Variant CNTNAP3:p.Leu1129Phe (chr9-39085791-C-G) – ACMG Classification: Likely_benign (-1 pts)

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 0P and 1B. BP4

The NM_033655.5(CNTNAP3):c.3387G>C(p.Leu1129Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

Frequency

Genomes: 𝑓 0.0000068 ( 0 hom., cov: 28)

Exomes 𝑓: 7.1e-7 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

CNTNAP3
NM_033655.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.64

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: Likely_benign. The variant received -1 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.36774948).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CNTNAP3	NM_033655.5 link	c.3387G>C	p.Leu1129Phe	missense_variant	Exon 21 of 24	ENST00000297668.11	NP_387504.2	Q9BZ76-1
CNTNAP3	NM_001393379.1 link	c.3144G>C	p.Leu1048Phe	missense_variant	Exon 20 of 23		NP_001380308.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CNTNAP3	ENST00000297668.11 link	c.3387G>C	p.Leu1129Phe	missense_variant	Exon 21 of 24	1	NM_033655.5	ENSP00000297668.6		Q9BZ76-1

Frequencies

GnomAD3 genomes

AF:

0.00000679

AC:

AN:

147184

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000251

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

7.06e-7

AC:

AN:

1417154

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

706272

show subpopulations

African (AFR)

AF:

0.0000314

AC:

AN:

31874

American (AMR)

AF:

0.00

AC:

AN:

44472

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25952

East Asian (EAS)

AF:

0.00

AC:

AN:

38402

South Asian (SAS)

AF:

0.00

AC:

AN:

83936

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52616

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4004

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1077534

Other (OTH)

AF:

0.00

AC:

AN:

58364

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

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.00000679

AC:

AN:

147184

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

71494

show subpopulations

African (AFR)

AF:

0.0000251

AC:

AN:

39896

American (AMR)

AF:

0.00

AC:

AN:

14908

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3448

East Asian (EAS)

AF:

0.00

AC:

AN:

4846

South Asian (SAS)

AF:

0.00

AC:

AN:

4514

European-Finnish (FIN)

AF:

0.00

AC:

AN:

9612

Middle Eastern (MID)

AF:

0.00

AC:

AN:

308

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

66712

Other (OTH)

AF:

0.00

AC:

AN:

2034

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

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.40

BayesDel_addAF

Benign

-0.019

BayesDel_noAF

Benign

-0.27

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.21

T;.

Eigen

Benign

-0.061

Eigen_PC

Benign

-0.037

FATHMM_MKL

Uncertain

0.78

LIST_S2

Uncertain

0.95

D;D

M_CAP

Uncertain

0.22

MetaRNN

Benign

0.37

T;T

MetaSVM

Uncertain

-0.25

MutationAssessor

Benign

1.9

L;.

PhyloP100

1.6

PrimateAI

Uncertain

0.67

PROVEAN

Benign

-2.1

N;N

REVEL

Uncertain

0.41

Sift

Benign

0.23

T;T

Sift4G

Benign

0.15

T;T

Polyphen

0.10

B;D

Vest4

0.47

MutPred

0.66

Gain of methylation at K1125 (P = 0.0698);.;

MVP

0.68

ClinPred

0.90

GERP RS

3.3

Varity_R

0.20

gMVP

0.37

Mutation Taster

=66/34

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over