chr9-39078834-C-G

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_033655.5(CNTNAP3):​c.3529G>C​(p.Ala1177Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000657 in 152,258 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 0.0000066 ( 0 hom., cov: 47)
Exomes 𝑓: 0.0000029 ( 0 hom. )
Failed GnomAD Quality Control

Consequence

CNTNAP3
NM_033655.5 missense

Scores

3
9
7

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.603
Variant links:
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]

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.3766688).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
CNTNAP3NM_033655.5 linkc.3529G>C p.Ala1177Pro missense_variant Exon 22 of 24 ENST00000297668.11 NP_387504.2 Q9BZ76-1
CNTNAP3NM_001393379.1 linkc.3286G>C p.Ala1096Pro missense_variant Exon 21 of 23 NP_001380308.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
CNTNAP3ENST00000297668.11 linkc.3529G>C p.Ala1177Pro missense_variant Exon 22 of 24 1 NM_033655.5 ENSP00000297668.6 Q9BZ76-1
CNTNAP3ENST00000377656.6 linkc.3286G>C p.Ala1096Pro missense_variant Exon 21 of 23 1 ENSP00000366884.2 A6NC89
CNTNAP3ENST00000477002.1 linkn.275G>C non_coding_transcript_exon_variant Exon 3 of 3 5
CNTNAP3ENST00000493965.5 linkn.274-378G>C intron_variant Intron 3 of 4 5

Frequencies

GnomAD3 genomes
AF:
0.00000657
AC:
1
AN:
152258
Hom.:
0
Cov.:
47
show subpopulations
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:
0.0000147
Gnomad OTH
AF:
0.00
GnomAD4 exome
Data not reliable, filtered out with message: AS_VQSR
AF:
0.00000290
AC:
4
AN:
1380900
Hom.:
0
Cov.:
175
AF XY:
0.00000293
AC XY:
2
AN XY:
681466
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000371
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.00000657
AC:
1
AN:
152258
Hom.:
0
Cov.:
47
AF XY:
0.00
AC XY:
0
AN XY:
74390
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000147
Gnomad4 OTH
AF:
0.00

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Apr 25, 2023
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.3529G>C (p.A1177P) alteration is located in exon 22 (coding exon 22) of the CNTNAP3 gene. This alteration results from a G to C substitution at nucleotide position 3529, causing the alanine (A) at amino acid position 1177 to be replaced by a proline (P). 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
Uncertain
0.091
D
BayesDel_noAF
Benign
-0.11
CADD
Benign
21
DANN
Uncertain
0.99
DEOGEN2
Benign
0.057
T;.
Eigen
Benign
-0.20
Eigen_PC
Benign
-0.42
FATHMM_MKL
Benign
0.17
N
LIST_S2
Uncertain
0.96
D;D
M_CAP
Pathogenic
0.38
D
MetaRNN
Benign
0.38
T;T
MetaSVM
Uncertain
0.21
D
MutationAssessor
Pathogenic
3.0
M;.
PrimateAI
Pathogenic
0.87
D
PROVEAN
Uncertain
-2.8
D;D
REVEL
Uncertain
0.48
Sift
Uncertain
0.0040
D;D
Sift4G
Uncertain
0.010
D;D
Polyphen
0.99
D;P
Vest4
0.25
MutPred
0.55
Gain of catalytic residue at A1177 (P = 0.0215);.;
MVP
0.80
ClinPred
0.80
D
GERP RS
2.6
Varity_R
0.23
gMVP
0.58

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.020
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs1410147674; hg19: chr9-39078831; API