rs12933808

Positions:

• chr16-76498686-A-C
• chr16-76498686-A-G
• chr16-76498686-A-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The ENST00000611870.5(CNTNAP4):​c.2357A>C​(p.Gln786Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts 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. Q786R) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: CNTNAP4 ENST00000611870.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0370

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]

ACMG classification

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=0.19229028).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CNTNAP4	NM_033401.5	c.2357A>C	p.Gln786Pro	missense_variant	15/24	ENST00000611870.5	NP_207837.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CNTNAP4	ENST00000611870.5	c.2357A>C	p.Gln786Pro	missense_variant	15/24	1	NM_033401.5	ENSP00000479811	P4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 39

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.43
BayesDel_addAF	Pathogenic	0.29	D
BayesDel_noAF	Pathogenic	0.17
CADD	Benign	9.7
DANN	Benign	0.93
DEOGEN2	Benign	0.16	T;T;T;.;.;.
Eigen	Benign	-0.90
Eigen_PC	Benign	-0.95
FATHMM_MKL	Benign	0.086	N
LIST_S2	Uncertain	0.92	D;D;D;D;D;D
M_CAP	Benign	0.062	D
MetaRNN	Benign	0.19	T;T;T;T;T;T
MetaSVM	Benign	-0.75	T
MutationTaster	Benign	1.0	N;N;N;N
PrimateAI	Benign	0.23	T
PROVEAN	Uncertain	-2.8	.;.;.;.;D;D
REVEL	Uncertain	0.53
Sift	Benign	0.089	.;.;.;.;T;T
Sift4G	Benign	0.12	T;T;T;T;T;T
Polyphen		0.14	B;.;.;.;.;B
Vest4		0.51
MutPred		0.61		.;.;.;.;.;Gain of catalytic residue at L786 (P = 0.1979);
MVP		0.59
MPC		0.044
ClinPred		0.12	T
GERP RS		-0.49
Varity_R		0.10
gMVP		0.60

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

Other links and lift over

dbSNP: rs12933808; hg19: chr16-76532583;