dbSNP rs34165507: CNTNAP5:p.Thr1196Lys (chr2-124903032-C-A) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001367498.1(CNTNAP5):c.3587C>A(p.Thr1196Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000275 in 1,455,496 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000027 ( 0 hom. )

Consequence

CNTNAP5
NM_001367498.1 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.0740

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_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.06426555).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CNTNAP5	NM_001367498.1 link	c.3587C>A	p.Thr1196Lys	missense_variant	Exon 22 of 24	ENST00000682447.1	NP_001354427.1
CNTNAP5	NM_130773.4 link	c.3584C>A	p.Thr1195Lys	missense_variant	Exon 22 of 24		NP_570129.1	Q8WYK1
CNTNAP5	XM_017003316.2 link	c.3347C>A	p.Thr1116Lys	missense_variant	Exon 21 of 23		XP_016858805.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CNTNAP5	ENST00000682447.1 link	c.3587C>A	p.Thr1196Lys	missense_variant	Exon 22 of 24		NM_001367498.1	ENSP00000508115.1		A0A804HKY0
CNTNAP5	ENST00000431078.1 link	c.3584C>A	p.Thr1195Lys	missense_variant	Exon 22 of 24	1		ENSP00000399013.1		Q8WYK1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000168

AC:

AN:

237804

Hom.:

AF XY:

0.0000155

AC XY:

AN XY:

128688

show subpopulations

Gnomad AFR exome

AF:

0.0000688

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000103

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000275

AC:

AN:

1455496

Hom.:

Cov.:

AF XY:

0.00000415

AC XY:

AN XY:

723428

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:

0.0000470

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000378

ExAC

AF:

0.0000248

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.086

BayesDel_addAF

Benign

-0.22

BayesDel_noAF

Benign

-0.35

CADD

Benign

3.6

DANN

Benign

0.62

DEOGEN2

Benign

0.045

Eigen

Benign

-1.5

Eigen_PC

Benign

-1.6

FATHMM_MKL

Benign

0.050

LIST_S2

Benign

0.38

M_CAP

Benign

0.064

MetaRNN

Benign

0.064

MetaSVM

Benign

-0.64

MutationAssessor

Uncertain

2.8

PrimateAI

Benign

0.33

PROVEAN

Benign

-2.1

REVEL

Uncertain

0.33

Sift

Benign

0.040

Sift4G

Benign

0.074

Polyphen

0.0

Vest4

0.29

MutPred

0.55

Gain of ubiquitination at T1195 (P = 0.009);

MVP

0.17

MPC

0.10

ClinPred

0.064

GERP RS

-5.5

Varity_R

0.096

gMVP

0.55

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