Variant 2-124025707-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate

The NM_001367498.1(CNTNAP5):c.57G>T(p.Trp19Cys) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Consequence

CNTNAP5
NM_001367498.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.96

Variant links:

Genes affected

CNTNAP5 (HGNC:18748): (contactin associated protein family member 5) This gene product belongs to the neurexin family, members of which function in the vertebrate nervous system as cell adhesion molecules and receptors. This protein, like other neurexin proteins, 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. [provided by RefSeq, Jul 2008]

CNTNAP5 links:

CNTNAP5 (HGNC:):

CNTNAP5 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.892

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CNTNAP5	NM_001367498.1 linkuse as main transcript	c.57G>T	p.Trp19Cys	missense_variant	1/24	ENST00000682447.1	NP_001354427.1
CNTNAP5	NM_130773.4 linkuse as main transcript	c.57G>T	p.Trp19Cys	missense_variant	1/24		NP_570129.1	Q8WYK1
CNTNAP5	XM_017003316.2 linkuse as main transcript	c.57G>T	p.Trp19Cys	missense_variant	1/23		XP_016858805.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
CNTNAP5	ENST00000682447.1 linkuse as main transcript	c.57G>T	p.Trp19Cys	missense_variant	1/24		NM_001367498.1	ENSP00000508115.1	A0A804HKY0
CNTNAP5	ENST00000431078.1 linkuse as main transcript	c.57G>T	p.Trp19Cys	missense_variant	1/24	1		ENSP00000399013.1	Q8WYK1
CNTNAP5	ENST00000423939.2 linkuse as main transcript	n.421G>T		non_coding_transcript_exon_variant	1/2	4

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000402

AC:

AN:

248966

Hom.:

AF XY:

0.00000740

AC XY:

AN XY:

135072

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:

0.00000887

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

Cov.:

GnomAD4 genome

Cov.:

ExAC

AF:

0.00000827

AC:

EpiCase

AF:

0.0000545

EpiControl

AF:

0.00

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

Sep 27, 2021

The c.57G>T (p.W19C) alteration is located in exon 1 (coding exon 1) of the CNTNAP5 gene. This alteration results from a G to T substitution at nucleotide position 57, causing the tryptophan (W) at amino acid position 19 to be replaced by a cysteine (C). 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

0.25

BayesDel_addAF

Pathogenic

0.22

BayesDel_noAF

Uncertain

0.080

CADD

Pathogenic

DANN

Uncertain

0.99

DEOGEN2

Benign

0.19

Eigen

Uncertain

0.55

Eigen_PC

Uncertain

0.56

FATHMM_MKL

Benign

0.015

LIST_S2

Benign

0.74

M_CAP

Uncertain

0.18

MetaRNN

Pathogenic

0.89

MetaSVM

Uncertain

0.36

MutationAssessor

Uncertain

2.6

MutationTaster

Benign

1.0

PrimateAI

Uncertain

0.59

PROVEAN

Uncertain

-2.9

REVEL

Pathogenic

0.76

Sift

Uncertain

0.0010

Sift4G

Benign

0.10

Polyphen

0.99

Vest4

0.59

MutPred

0.77

Gain of disorder (P = 0.1733);

MVP

0.82

MPC

0.54

ClinPred

0.97

GERP RS

4.5

Varity_R

0.35

gMVP

0.46

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.25

Details are displayed if max score is > 0.2

DS_AG_spliceai

0.25

Position offset: 8

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