Variant 16-76449739-C-T 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.952C>T(p.Pro318Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000416 in 1,441,472 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/17 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000042 ( 0 hom. )

Consequence

CNTNAP4
NM_033401.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.989

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 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=0.20751408).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CNTNAP4	NM_033401.5 linkuse as main transcript	c.952C>T	p.Pro318Ser	missense_variant	7/24	ENST00000611870.5	NP_207837.2	Q9C0A0-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CNTNAP4	ENST00000611870.5 linkuse as main transcript	c.952C>T	p.Pro318Ser	missense_variant	7/24	1	NM_033401.5	ENSP00000479811.1		Q9C0A0-1
ENSG00000287694	ENST00000655556.1 linkuse as main transcript	n.952C>T		non_coding_transcript_exon_variant	7/25			ENSP00000499374.1		A0A590UJB1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000451

AC:

AN:

221522

Hom.:

AF XY:

0.00000845

AC XY:

AN XY:

118404

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000103

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000416

AC:

AN:

1441472

Hom.:

Cov.:

AF XY:

0.00000560

AC XY:

AN XY:

714690

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000242

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000363

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

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

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Mar 21, 2023

The c.952C>T (p.P318S) alteration is located in exon 7 (coding exon 7) of the CNTNAP4 gene. This alteration results from a C to T substitution at nucleotide position 952, causing the proline (P) at amino acid position 318 to be replaced by a serine (S). 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

0.080

BayesDel_addAF

Benign

-0.051

BayesDel_noAF

Benign

-0.31

CADD

Benign

DANN

Benign

0.97

DEOGEN2

Benign

0.34

T;T;.

Eigen

Benign

-0.19

Eigen_PC

Benign

-0.041

FATHMM_MKL

Uncertain

0.92

LIST_S2

Benign

0.85

D;D;D

M_CAP

Benign

0.044

MetaRNN

Benign

0.21

T;T;T

MetaSVM

Benign

-0.82

PROVEAN

Uncertain

-3.6

.;.;D

REVEL

Uncertain

0.30

Sift

Benign

0.49

.;.;T

Sift4G

Benign

0.55

T;T;T

Polyphen

0.013

B;.;B

Vest4

0.27

MutPred

0.43

.;.;Gain of glycosylation at P321 (P = 0.0219);

MVP

0.75

ClinPred

0.40

GERP RS

3.4

Varity_R

0.078

gMVP

0.20

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

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over