9-39085791-C-A

Variant names:

• chr9-39085791-C-A
• rs1386062130
• NM_033655.5:c.3387G>T

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_033655.5(CNTNAP3):​c.3387G>T​(p.Leu1129Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000575 in 1,564,338 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.0000068 (0 hom., cov: 28)
  • Exomes 𝑓: 0.0000056 (0 hom.)
• Consequence: CNTNAP3 NM_033655.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.64
• Publications: 0 publications found

Genes affected

CNTNAP3 (HGNC:13834): (contactin associated protein family member 3) The protein encoded by this gene belongs to the NCP family of cell-recognition molecules. This family represents a distinct subgroup of the neurexins. NCP proteins mediate neuron-glial interactions in vertebrates and glial-glial contact in invertebrates. The protein encoded by this gene may play a role in cell recognition within the nervous system. Alternatively spliced transcript variants encoding different isoforms have been described but their biological nature has not been determined. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.36988398).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CNTNAP3	NM_033655.5	c.3387G>T	p.Leu1129Phe	missense_variant	Exon 21 of 24	ENST00000297668.11	NP_387504.2
CNTNAP3	NM_001393379.1	c.3144G>T	p.Leu1048Phe	missense_variant	Exon 20 of 23		NP_001380308.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CNTNAP3	ENST00000297668.11	c.3387G>T	p.Leu1129Phe	missense_variant	Exon 21 of 24	1	NM_033655.5	ENSP00000297668.6

Frequencies

GnomAD3 genomes AF: 0.00000679 AC: 1 AN: 147184 Hom.: 0 Cov.: 28

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000150

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.00000565 AC: 8 AN: 1417154 Hom.: 0 Cov.: 31 AF XY: 0.00000850 AC XY: 6 AN XY: 706272

African (AFR) AF: 0.00 AC: 0 AN: 31874

American (AMR) AF: 0.00 AC: 0 AN: 44472

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25952

East Asian (EAS) AF: 0.00 AC: 0 AN: 38402

South Asian (SAS) AF: 0.00 AC: 0 AN: 83936

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52616

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4004

European-Non Finnish (NFE) AF: 0.00000742 AC: 8 AN: 1077534

Other (OTH) AF: 0.00 AC: 0 AN: 58364

GnomAD4 genome AF: 0.00000679 AC: 1 AN: 147184 Hom.: 0 Cov.: 28 AF XY: 0.00 AC XY: 0 AN XY: 71494

African (AFR) AF: 0.00 AC: 0 AN: 39896

American (AMR) AF: 0.00 AC: 0 AN: 14908

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3448

East Asian (EAS) AF: 0.00 AC: 0 AN: 4846

South Asian (SAS) AF: 0.00 AC: 0 AN: 4514

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 9612

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 308

European-Non Finnish (NFE) AF: 0.0000150 AC: 1 AN: 66712

Other (OTH) AF: 0.00 AC: 0 AN: 2034

Alfa AF: 0.00 Hom.: 0

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Apr 16, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.3387G>T (p.L1129F) alteration is located in exon 21 (coding exon 21) of the CNTNAP3 gene. This alteration results from a G to T substitution at nucleotide position 3387, causing the leucine (L) at amino acid position 1129 to be replaced by a phenylalanine (F). 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	Uncertain	0.40
BayesDel_addAF	Benign	-0.019	T
BayesDel_noAF	Benign	-0.27
CADD	Benign	16
DANN	Uncertain	1.0
DEOGEN2	Benign	0.21	T;.
Eigen	Benign	-0.061
Eigen_PC	Benign	-0.037
FATHMM_MKL	Uncertain	0.79	D
LIST_S2	Uncertain	0.95	D;D
M_CAP	Uncertain	0.23	D
MetaRNN	Benign	0.37	T;T
MetaSVM	Uncertain	-0.25	T
MutationAssessor	Benign	1.9	L;.
PhyloP100		1.6
PrimateAI	Uncertain	0.67	T
PROVEAN	Benign	-2.1	N;N
REVEL	Uncertain	0.41
Sift	Benign	0.23	T;T
Sift4G	Benign	0.15	T;T
Polyphen		0.10	B;D
Vest4		0.47
MutPred		0.66		Gain of methylation at K1125 (P = 0.0698);.;
MVP		0.68
ClinPred		0.90	D
GERP RS		3.3
Varity_R		0.20
gMVP		0.37
Mutation Taster		=66/34	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.10		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: rs1386062130; hg19: chr9-39085788;