Variant 16-76553305-T-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 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. 14/20 in silico tools predict 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 same amino acid change has been previously reported as Likely benignin UniProt.

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

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:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CNTNAP4	NM_033401.5 linkuse as main transcript	c.3465T>A	p.Asp1155Glu	missense_variant	22/24	ENST00000611870.5	NP_207837.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CNTNAP4	ENST00000611870.5 linkuse as main transcript	c.3465T>A	p.Asp1155Glu	missense_variant	22/24	1	NM_033401.5	ENSP00000479811	P4	Q9C0A0-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000407

AC:

AN:

245814

Hom.:

AF XY:

0.00000750

AC XY:

AN XY:

133412

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 SAS exome

AF:

0.00

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

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000253

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.060

BayesDel_addAF

Benign

-0.46

BayesDel_noAF

Benign

-0.72

CADD

Benign

1.2

DANN

Benign

0.70

DEOGEN2

Benign

0.062

T;T;T;.;.;.

Eigen

Benign

-0.68

Eigen_PC

Benign

-0.54

FATHMM_MKL

Uncertain

0.81

LIST_S2

Benign

0.064

T;T;T;T;T;T

M_CAP

Benign

0.0024

MetaRNN

Benign

0.070

T;T;T;T;T;T

MetaSVM

Benign

-0.99

MutationTaster

Benign

1.0

P;P;P;P

PrimateAI

Benign

0.46

PROVEAN

Benign

1.0

.;.;.;.;N;N

REVEL

Benign

0.037

Sift

Benign

1.0

.;.;.;.;T;T

Sift4G

Benign

1.0

T;T;T;T;T;T

Polyphen

0.0

B;.;.;.;.;B

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over