Genetic Variant CNTNAP3:p.Ser1122Asn (chr9-39085813-C-T) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_033655.5(CNTNAP3):c.3365G>A(p.Ser1122Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000122 in 1,555,774 control chromosomes in the GnomAD database, including 7 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00010 ( 0 hom., cov: 31)

Exomes 𝑓: 0.00012 ( 7 hom. )

Consequence

CNTNAP3
NM_033655.5 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.23

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: Benign. The variant received -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.035443753).

BP6

Variant 9-39085813-C-T is Benign according to our data. Variant chr9-39085813-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 3146853.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAdExome4 at 7 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_033655.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CNTNAP3	NM_033655.5	MANE Select	c.3365G>A	p.Ser1122Asn	missense	Exon 21 of 24	NP_387504.2
	CNTNAP3	NM_001393379.1		c.3122G>A	p.Ser1041Asn	missense	Exon 20 of 23	NP_001380308.1	A6NC89

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CNTNAP3	ENST00000297668.11	TSL:1 MANE Select	c.3365G>A	p.Ser1122Asn	missense	Exon 21 of 24	ENSP00000297668.6	Q9BZ76-1
CNTNAP3	ENST00000377656.6	TSL:1	c.3122G>A	p.Ser1041Asn	missense	Exon 20 of 23	ENSP00000366884.2	A6NC89
CNTNAP3	ENST00000865312.1		c.3485G>A	p.Ser1162Asn	missense	Exon 22 of 25	ENSP00000535371.1

Frequencies

GnomAD3 genomes

AF:

0.0000999

AC:

AN:

150100

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000663

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:

0.000207

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.000137

AC:

AN:

240996

AF XY:

0.000123

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000147

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000255

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000124

AC:

175

AN:

1405674

Hom.:

Cov.:

AF XY:

0.000128

AC XY:

AN XY:

700474

show subpopulations

African (AFR)

AF:

0.0000331

AC:

AN:

30216

American (AMR)

AF:

0.0000904

AC:

AN:

44226

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25806

East Asian (EAS)

AF:

0.00

AC:

AN:

38094

South Asian (SAS)

AF:

0.00

AC:

AN:

82780

European-Finnish (FIN)

AF:

0.0000572

AC:

AN:

52404

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3966

European-Non Finnish (NFE)

AF:

0.000146

AC:

156

AN:

1070208

Other (OTH)

AF:

0.000190

AC:

AN:

57974

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.521

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

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

AF:

0.0000999

AC:

AN:

150100

Hom.:

Cov.:

AF XY:

0.0000410

AC XY:

AN XY:

73094

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

40704

American (AMR)

AF:

0.0000663

AC:

AN:

15094

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3464

East Asian (EAS)

AF:

0.00

AC:

AN:

5048

South Asian (SAS)

AF:

0.00

AC:

AN:

4686

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10158

Middle Eastern (MID)

AF:

0.00

AC:

AN:

314

European-Non Finnish (NFE)

AF:

0.000207

AC:

AN:

67646

Other (OTH)

AF:

0.00

AC:

AN:

2074

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.565

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome 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

Alfa

AF:

0.000185

Hom.:

Bravo

AF:

0.0000945

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000118

AC:

ExAC

AF:

0.000176

AC:

ClinVar

ClinVar submissions

Significance:Likely benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.068

BayesDel_addAF

Benign

-0.41

BayesDel_noAF

Benign

-0.53

CADD

Benign

9.1

(source)

DANN

Benign

0.26

DEOGEN2

Benign

0.048

Eigen

Benign

-0.72

Eigen_PC

Benign

-0.57

FATHMM_MKL

Benign

0.15

LIST_S2

Benign

0.40

M_CAP

Benign

0.038

MetaRNN

Benign

0.035

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-0.33

PhyloP100

1.2

PrimateAI

Uncertain

0.59

PROVEAN

Benign

1.1

REVEL

Benign

0.10

Sift

Benign

1.0

Sift4G

Benign

1.0

Polyphen

0.0020

Vest4

0.12

MVP

0.50

ClinPred

0.016

GERP RS

1.2

Varity_R

0.035

gMVP

0.095

Mutation Taster

=97/3

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

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over