NM_033401.5:c.1813G>C

Variant names:

• chr16-76479469-G-C
• NM_033401.5:c.1813G>C

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_033401.5(CNTNAP4):​c.1813G>C​(p.Gly605Arg) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: CNTNAP4 NM_033401.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 9.92
• Publications: 0 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 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.862

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.1813G>C	p.Gly605Arg	missense	Exon 12 of 24	NP_207837.2	Q9C0A0-1
	CNTNAP4	NM_001322181.2		c.1810G>C	p.Gly604Arg	missense	Exon 12 of 24	NP_001309110.1
	CNTNAP4	NM_001322188.2		c.1813G>C	p.Gly605Arg	missense	Exon 12 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.1813G>C	p.Gly605Arg	missense	Exon 12 of 24	ENSP00000479811.1	Q9C0A0-1
	CNTNAP4	ENST00000622250.4	TSL:1	c.1669G>C	p.Gly557Arg	missense	Exon 11 of 23	ENSP00000477698.1	A0A087WTA1
	ENSG00000287694	ENST00000655556.1		n.1813G>C		non_coding_transcript_exon	Exon 12 of 25	ENSP00000499374.1	A0A590UJB1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 29

GnomAD4 genome Cov.: 33

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.39
BayesDel_addAF	Pathogenic	0.27	D
BayesDel_noAF	Pathogenic	0.15
CADD	Pathogenic	28
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.19	T
Eigen	Pathogenic	0.83
Eigen_PC	Pathogenic	0.85
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Pathogenic	0.99	D
M_CAP	Uncertain	0.088	D
MetaRNN	Pathogenic	0.86	D
MetaSVM	Benign	-0.63	T
PhyloP100		9.9
PrimateAI	Uncertain	0.76	T
PROVEAN	Pathogenic	-6.7	D
REVEL	Uncertain	0.56
Sift	Uncertain	0.0010	D
Sift4G	Pathogenic	0.0010	D
Polyphen		0.97	D
Vest4		0.90
MutPred		0.67		Loss of glycosylation at S607 (P = 0.044)
MVP		0.73
MPC		0.15
ClinPred		1.0	D
GERP RS		5.6
Varity_R		0.31
gMVP		0.72

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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

hg19: chr16-76513366;