16-76498686-A-C

Variant names:

• chr16-76498686-A-C
• rs12933808
• NM_033401.5:c.2357A>C

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_033401.5(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.

• Frequency: Genomes: not found (cov: 32)
• Consequence: CNTNAP4 NM_033401.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0370
• Publications: 25 publications found

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]

ENSG00000287694 (HGNC:):

ACMG classification

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=0.19229028).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_033401.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CNTNAP4	NM_033401.5	MANE Select	c.2357A>C	p.Gln786Pro	missense	Exon 15 of 24	NP_207837.2	Q9C0A0-1
	CNTNAP4	NM_001322181.2		c.2354A>C	p.Gln785Pro	missense	Exon 15 of 24	NP_001309110.1
	CNTNAP4	NM_001322188.2		c.2357A>C	p.Gln786Pro	missense	Exon 15 of 25	NP_001309117.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CNTNAP4	ENST00000611870.5	TSL:1 MANE Select	c.2357A>C	p.Gln786Pro	missense	Exon 15 of 24	ENSP00000479811.1	Q9C0A0-1
	CNTNAP4	ENST00000622250.4	TSL:1	c.2213A>C	p.Gln738Pro	missense	Exon 14 of 23	ENSP00000477698.1	A0A087WTA1
	ENSG00000287694	ENST00000655556.1		n.2357A>C		non_coding_transcript_exon	Exon 15 of 25	ENSP00000499374.1	A0A590UJB1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 39

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

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
Eigen	Benign	-0.90
Eigen_PC	Benign	-0.95
FATHMM_MKL	Benign	0.086	N
LIST_S2	Uncertain	0.92	D
M_CAP	Benign	0.062	D
MetaRNN	Benign	0.19	T
MetaSVM	Benign	-0.75	T
PhyloP100		0.037
PrimateAI	Benign	0.23	T
PROVEAN	Uncertain	-2.8	D
REVEL	Uncertain	0.53
Sift	Benign	0.089	T
Sift4G	Benign	0.12	T
Polyphen		0.14	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

Other links and lift over

dbSNP: rs12933808; hg19: chr16-76532583;