9-39088451-T-A

Variant names:

• chr9-39088451-T-A
• NM_033655.5:c.3192A>T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_033655.5(CNTNAP3):​c.3192A>T​(p.Glu1064Asp) 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. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: CNTNAP3 NM_033655.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.588

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

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.14040402).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CNTNAP3	NM_033655.5	c.3192A>T	p.Glu1064Asp	missense_variant	Exon 19 of 24	ENST00000297668.11	NP_387504.2
CNTNAP3	NM_001393379.1	c.2949A>T	p.Glu983Asp	missense_variant	Exon 18 of 23		NP_001380308.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CNTNAP3	ENST00000297668.11	c.3192A>T	p.Glu1064Asp	missense_variant	Exon 19 of 24	1	NM_033655.5	ENSP00000297668.6
CNTNAP3	ENST00000377656.6	c.2949A>T	p.Glu983Asp	missense_variant	Exon 18 of 23	1		ENSP00000366884.2
CNTNAP3	ENST00000358144.6	c.2928A>T	p.Glu976Asp	missense_variant	Exon 17 of 18	5		ENSP00000350863.2
CNTNAP3	ENST00000493965.5	n.23A>T		non_coding_transcript_exon_variant	Exon 1 of 5	5

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 6.95e-7 AC: 1 AN: 1438884 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 716098

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: 9.04e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 31

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

May 31, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.3192A>T (p.E1064D) alteration is located in exon 19 (coding exon 19) of the CNTNAP3 gene. This alteration results from a A to T substitution at nucleotide position 3192, causing the glutamic acid (E) at amino acid position 1064 to be replaced by an aspartic acid (D). 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	0.45
BayesDel_addAF	Uncertain	0.020	T
BayesDel_noAF	Benign	-0.21
CADD	Benign	14
DANN	Benign	0.70
DEOGEN2	Benign	0.077	T;.;.
Eigen	Benign	-0.93
Eigen_PC	Benign	-0.96
FATHMM_MKL	Benign	0.13	N
LIST_S2	Uncertain	0.88	D;D;D
M_CAP	Benign	0.025	T
MetaRNN	Benign	0.14	T;T;T
MetaSVM	Benign	-0.64	T
MutationAssessor	Benign	1.3	L;.;.
PrimateAI	Uncertain	0.61	T
PROVEAN	Benign	-1.3	N;N;N
REVEL	Uncertain	0.44
Sift	Benign	0.73	T;T;T
Sift4G	Benign	0.57	T;T;T
Polyphen		0.024	B;D;.
Vest4		0.24
MutPred		0.78		Gain of sheet (P = 0.0827);.;.;
MVP		0.36
ClinPred		0.27	T
GERP RS		-3.4
Varity_R		0.060
gMVP		0.35

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		Details are displayed if max score is > 0.2

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr9-39088448;