Genetic Variant NM_001367498.1:c.484A>G (chr2-124417545-A-G) – 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_001367498.1(CNTNAP5):c.484A>G(p.Ser162Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,468 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/22 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 variant affecting the same amino acid position, but resulting in a different missense (i.e. S162R) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 31)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

CNTNAP5
NM_001367498.1 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.97

Publications

0 publications found

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 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=0.19396114).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CNTNAP5	NM_001367498.1 link	c.484A>G	p.Ser162Gly	missense_variant	Exon 4 of 24	ENST00000682447.1	NP_001354427.1
CNTNAP5	NM_130773.4 link	c.484A>G	p.Ser162Gly	missense_variant	Exon 4 of 24		NP_570129.1	Q8WYK1
CNTNAP5	XM_017003316.2 link	c.484A>G	p.Ser162Gly	missense_variant	Exon 4 of 23		XP_016858805.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CNTNAP5	ENST00000682447.1 link	c.484A>G	p.Ser162Gly	missense_variant	Exon 4 of 24		NM_001367498.1	ENSP00000508115.1		A0A804HKY0
CNTNAP5	ENST00000431078.1 link	c.484A>G	p.Ser162Gly	missense_variant	Exon 4 of 24	1		ENSP00000399013.1		Q8WYK1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461468

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

727002

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33480

American (AMR)

AF:

0.0000224

AC:

AN:

44684

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26122

East Asian (EAS)

AF:

0.00

AC:

AN:

39692

South Asian (SAS)

AF:

0.00

AC:

AN:

86176

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53396

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1111776

Other (OTH)

AF:

0.00

AC:

AN:

60374

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

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.064

BayesDel_addAF

Uncertain

0.033

BayesDel_noAF

Benign

-0.19

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.39

Eigen

Benign

-0.54

Eigen_PC

Benign

-0.38

FATHMM_MKL

Benign

0.11

LIST_S2

Benign

0.73

M_CAP

Benign

0.031

MetaRNN

Benign

0.19

MetaSVM

Uncertain

-0.052

MutationAssessor

Benign

0.14

PhyloP100

3.0

PrimateAI

Benign

0.38

PROVEAN

Benign

-1.5

REVEL

Uncertain

0.37

Sift

Benign

0.17

Sift4G

Benign

0.28

Polyphen

0.0010

Vest4

0.23

MutPred

0.47

Loss of solvent accessibility (P = 0.0364);

MVP

0.43

MPC

0.078

ClinPred

0.27

GERP RS

6.2

Varity_R

0.14

gMVP

0.21

Mutation Taster

=93/7

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over