Genetic Variant NM_033401.5:c.3465T>A (chr16-76553305-T-A) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_033401.5(CNTNAP4):c.3465T>A(p.Asp1155Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 6.9e-7 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

CNTNAP4
NM_033401.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.0640

Publications

25 publications found

Variant links:

Genes affected

CNTNAP4 (HGNC:18747): (contactin associated protein family member 4) This gene encodes a member of the neurexin protein family. Members of this family function in the vertebrate nervous system as cell adhesion molecules and receptors. This protein contains epidermal growth factor repeats and laminin G domains. In addition, it includes an F5/8 type C domain, discoidin/neuropilin- and fibrinogen-like domains, and thrombospondin N-terminal-like domains. This protein may also play a role in proper neurotransmission in the dopaminergic and GABAergic systems and mutations in this gene may be associated with certain psychiatric illnesses. A polymorphism in an intron of this gene may be associated with longevity. [provided by RefSeq, Apr 2016]

CNTNAP4 links:

ENSG00000287694 (HGNC:):

ENSG00000287694 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.069631666).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_033401.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CNTNAP4	NM_033401.5	MANE Select	c.3465T>A	p.Asp1155Glu	missense	Exon 22 of 24	NP_207837.2	Q9C0A0-1
CNTNAP4	NM_001322181.2		c.3462T>A	p.Asp1154Glu	missense	Exon 22 of 24	NP_001309110.1
CNTNAP4	NM_001322188.2		c.3465T>A	p.Asp1155Glu	missense	Exon 22 of 25	NP_001309117.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CNTNAP4	ENST00000611870.5	TSL:1 MANE Select	c.3465T>A	p.Asp1155Glu	missense	Exon 22 of 24	ENSP00000479811.1	Q9C0A0-1
CNTNAP4	ENST00000622250.4	TSL:1	c.3321T>A	p.Asp1107Glu	missense	Exon 21 of 23	ENSP00000477698.1	A0A087WTA1
ENSG00000287694	ENST00000655556.1		n.3465T>A		non_coding_transcript_exon	Exon 22 of 25	ENSP00000499374.1	A0A590UJB1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000407

AC:

AN:

245814

AF XY:

0.00000750

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000562

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

6.87e-7

AC:

AN:

1455728

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

723116

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33346

American (AMR)

AF:

0.00

AC:

AN:

44516

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26080

East Asian (EAS)

AF:

0.0000253

AC:

AN:

39520

South Asian (SAS)

AF:

0.00

AC:

AN:

85952

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53330

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5738

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1107146

Other (OTH)

AF:

0.00

AC:

AN:

60100

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.575

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.:

Alfa

AF:

0.00

Hom.:

31778

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.060

BayesDel_addAF

Benign

-0.46

BayesDel_noAF

Benign

-0.72

CADD

Benign

1.2

(source)

DANN

Benign

0.70

DEOGEN2

Benign

0.062

Eigen

Benign

-0.68

Eigen_PC

Benign

-0.54

FATHMM_MKL

Uncertain

0.81

LIST_S2

Benign

0.064

M_CAP

Benign

0.0024

MetaRNN

Benign

0.070

MetaSVM

Benign

-0.99

PhyloP100

-0.064

PrimateAI

Benign

0.46

PROVEAN

Benign

1.0

REVEL

Benign

0.037

Sift

Benign

1.0

Sift4G

Benign

1.0

Polyphen

0.0

Vest4

0.047

MutPred

0.30

Gain of disorder (P = 0.1807)

MVP

0.49

MPC

0.021

ClinPred

0.035

GERP RS

3.3

Varity_R

0.043

gMVP

0.16

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