16-76467370-T-C

Variant names:

• chr16-76467370-T-C
• NM_033401.5:c.1502T>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.1502T>C​(p.Phe501Ser) 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. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: CNTNAP4 NM_033401.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.139

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=0.08442095).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CNTNAP4	NM_033401.5	c.1502T>C	p.Phe501Ser	missense_variant	Exon 10 of 24	ENST00000611870.5	NP_207837.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CNTNAP4	ENST00000611870.5	c.1502T>C	p.Phe501Ser	missense_variant	Exon 10 of 24	1	NM_033401.5	ENSP00000479811.1
ENSG00000287694	ENST00000655556.1	n.1502T>C		non_coding_transcript_exon_variant	Exon 10 of 25			ENSP00000499374.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

May 01, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.1502T>C (p.F501S) alteration is located in exon 10 (coding exon 10) of the CNTNAP4 gene. This alteration results from a T to C substitution at nucleotide position 1502, causing the phenylalanine (F) at amino acid position 501 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.062
BayesDel_addAF	Benign	-0.13	T
BayesDel_noAF	Benign	-0.43
CADD	Benign	15
DANN	Benign	0.68
DEOGEN2	Benign	0.0026	T;T;T;.;.;.
Eigen	Benign	-0.60
Eigen_PC	Benign	-0.48
FATHMM_MKL	Benign	0.14	N
LIST_S2	Benign	0.095	T;T;T;T;T;T
M_CAP	Benign	0.022	T
MetaRNN	Benign	0.084	T;T;T;T;T;T
MetaSVM	Benign	-0.97	T
PhyloP100		0.14
PrimateAI	Benign	0.39	T
PROVEAN	Benign	2.0	.;.;.;.;N;N
REVEL	Benign	0.14
Sift	Benign	1.0	.;.;.;.;T;T
Sift4G	Benign	1.0	T;T;T;T;T;T
Polyphen		0.0020	B;.;.;.;.;B
Vest4		0.17
MutPred		0.46		.;.;.;.;.;Gain of disorder (P = 0.0079);
MVP		0.67
MPC		0.026
ClinPred		0.18	T
GERP RS		3.1
Varity_R		0.14
gMVP		0.35

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Other links and lift over

hg19: chr16-76501267;