Variant 2-124417518-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2PP3_Strong

The NM_001367498.1(CNTNAP5):c.457C>T(p.Arg153Cys) variant causes a missense change. The variant allele was found at a frequency of 0.00000342 in 1,461,546 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 31)

Exomes 𝑓: 0.0000034 ( 0 hom. )

Consequence

CNTNAP5
NM_001367498.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.91

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:

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ACMG classification

Classification made for transcript

Verdict is Likely_pathogenic. Variant got 6 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.989

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CNTNAP5	NM_001367498.1 link	c.457C>T	p.Arg153Cys	missense_variant	4/24	ENST00000682447.1	NP_001354427.1
CNTNAP5	NM_130773.4 link	c.457C>T	p.Arg153Cys	missense_variant	4/24		NP_570129.1	Q8WYK1
CNTNAP5	XM_017003316.2 link	c.457C>T	p.Arg153Cys	missense_variant	4/23		XP_016858805.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CNTNAP5	ENST00000682447.1 link	c.457C>T	p.Arg153Cys	missense_variant	4/24		NM_001367498.1	ENSP00000508115.1		A0A804HKY0
CNTNAP5	ENST00000431078.1 link	c.457C>T	p.Arg153Cys	missense_variant	4/24	1		ENSP00000399013.1		Q8WYK1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000342

AC:

AN:

1461546

Hom.:

Cov.:

AF XY:

0.00000275

AC XY:

AN XY:

727024

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:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000450

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

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

Nov 26, 2024

The c.457C>T (p.R153C) alteration is located in exon 4 (coding exon 4) of the CNTNAP5 gene. This alteration results from a C to T substitution at nucleotide position 457, causing the arginine (R) at amino acid position 153 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

Uncertain

0.46

BayesDel_addAF

Pathogenic

0.54

BayesDel_noAF

Pathogenic

0.54

CADD

Pathogenic

DANN

Pathogenic

1.0

DEOGEN2

Pathogenic

0.80

Eigen

Pathogenic

1.1

Eigen_PC

Pathogenic

1.0

FATHMM_MKL

Uncertain

0.97

LIST_S2

Pathogenic

0.98

M_CAP

Pathogenic

0.78

MetaRNN

Pathogenic

0.99

MetaSVM

Pathogenic

1.0

MutationAssessor

Pathogenic

4.7

PrimateAI

Uncertain

0.68

PROVEAN

Pathogenic

-7.4

REVEL

Pathogenic

0.87

Sift

Uncertain

0.0010

Sift4G

Pathogenic

0.0

Polyphen

1.0

Vest4

0.99

MutPred

0.85

Loss of MoRF binding (P = 9e-04);

MVP

0.76

MPC

0.54

ClinPred

1.0

GERP RS

6.2

Varity_R

0.55

gMVP

0.85

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

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over