chr9-39078846-A-G

Variant names:

• chr9-39078846-A-G
• rs1381493482
• NM_033655.5:c.3517T>C

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_033655.5(CNTNAP3):​c.3517T>C​(p.Phe1173Leu) variant causes a missense change. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.48 (0 hom., cov: 47)
  • Exomes 𝑓: 0.48 (1 hom.)
  • Failed GnomAD Quality Control
• Consequence: CNTNAP3 NM_033655.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.18
• Publications: 2 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: Likely_benign. The variant received -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.25744528).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CNTNAP3	NM_033655.5	c.3517T>C	p.Phe1173Leu	missense_variant	Exon 22 of 24	ENST00000297668.11	NP_387504.2
CNTNAP3	NM_001393379.1	c.3274T>C	p.Phe1092Leu	missense_variant	Exon 21 of 23		NP_001380308.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CNTNAP3	ENST00000297668.11	c.3517T>C	p.Phe1173Leu	missense_variant	Exon 22 of 24	1	NM_033655.5	ENSP00000297668.6
CNTNAP3	ENST00000377656.6	c.3274T>C	p.Phe1092Leu	missense_variant	Exon 21 of 23	1		ENSP00000366884.2
CNTNAP3	ENST00000477002.1	n.263T>C		non_coding_transcript_exon_variant	Exon 3 of 3	5
CNTNAP3	ENST00000493965.5	n.274-390T>C		intron_variant	Intron 3 of 4	5

Frequencies

GnomAD3 genomes AF: 0.482 AC: 63588 AN: 131958 Hom.: 0 Cov.: 47

Gnomad AFR AF: 0.485

Gnomad AMI AF: 0.484

Gnomad AMR AF: 0.471

Gnomad ASJ AF: 0.478

Gnomad EAS AF: 0.481

Gnomad SAS AF: 0.490

Gnomad FIN AF: 0.491

Gnomad MID AF: 0.471

Gnomad NFE AF: 0.480

Gnomad OTH AF: 0.476

GnomAD2 exomes AF: 0.000208 AC: 9 AN: 43186 AF XY: 0.0000874

Gnomad AFR exome AF: 0.000644

Gnomad AMR exome AF: 0.0000976

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000486

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000180

Gnomad OTH exome AF: 0.000670

GnomAD4 exome Data not reliable, filtered out with message: InbreedingCoeff AF: 0.479 AC: 570067 AN: 1190208 Hom.: 1 Cov.: 210 AF XY: 0.479 AC XY: 281817 AN XY: 588048

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.478 AC: 12749 AN: 26666

American (AMR) AF: 0.443 AC: 11480 AN: 25902

Ashkenazi Jewish (ASJ) AF: 0.463 AC: 9405 AN: 20334

East Asian (EAS) AF: 0.468 AC: 14042 AN: 29984

South Asian (SAS) AF: 0.485 AC: 33214 AN: 68502

European-Finnish (FIN) AF: 0.494 AC: 15507 AN: 31388

Middle Eastern (MID) AF: 0.456 AC: 1497 AN: 3282

European-Non Finnish (NFE) AF: 0.480 AC: 448544 AN: 934636

Other (OTH) AF: 0.477 AC: 23629 AN: 49514

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.000000), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR;InbreedingCoeff AF: 0.482 AC: 63628 AN: 132036 Hom.: 0 Cov.: 47 AF XY: 0.482 AC XY: 31137 AN XY: 64566

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.485 AC: 17717 AN: 36498

American (AMR) AF: 0.471 AC: 5938 AN: 12614

Ashkenazi Jewish (ASJ) AF: 0.478 AC: 1401 AN: 2928

East Asian (EAS) AF: 0.481 AC: 2161 AN: 4492

South Asian (SAS) AF: 0.490 AC: 2090 AN: 4262

European-Finnish (FIN) AF: 0.491 AC: 4694 AN: 9554

Middle Eastern (MID) AF: 0.477 AC: 105 AN: 220

European-Non Finnish (NFE) AF: 0.480 AC: 28294 AN: 58900

Other (OTH) AF: 0.476 AC: 840 AN: 1766

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0.000000), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.218 Hom.: 1

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Apr 02, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.3517T>C (p.F1173L) alteration is located in exon 22 (coding exon 22) of the CNTNAP3 gene. This alteration results from a T to C substitution at nucleotide position 3517, causing the phenylalanine (F) at amino acid position 1173 to be replaced by a leucine (L). 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	Pathogenic	0.90
BayesDel_addAF	Benign	-0.090	T
BayesDel_noAF	Benign	-0.37
CADD	Benign	11
DANN	Benign	0.88
DEOGEN2	Benign	0.39	T;.
Eigen	Benign	-0.58
Eigen_PC	Benign	-0.64
FATHMM_MKL	Benign	0.65	D
LIST_S2	Benign	0.72	T;T
M_CAP	Uncertain	0.093	D
MetaRNN	Benign	0.26	T;T
MetaSVM	Benign	-0.73	T
MutationAssessor	Benign	1.4	L;.
PhyloP100		4.2
PrimateAI	Pathogenic	0.94	D
PROVEAN	Uncertain	-3.5	D;D
REVEL	Benign	0.17
Sift	Benign	0.15	T;T
Sift4G	Uncertain	0.059	T;T
Polyphen		0.020	B;B
Vest4		0.32
MutPred		0.47		Loss of sheet (P = 0.0817);.;
MVP		0.71
ClinPred		0.038	T
GERP RS		1.5
Varity_R		0.19
gMVP		0.67
Mutation Taster		=86/14	polymorphism

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: rs1381493482; hg19: chr9-39078843; COSMIC: COSV52663165;