chr9-39086816-T-C

Variant names:

• chr9-39086816-T-C
• rs1369109182
• NM_033655.5:c.3254A>G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_033655.5(CNTNAP3):​c.3254A>G​(p.His1085Arg) 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. H1085P) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 29)
• Consequence: CNTNAP3 NM_033655.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.45
• 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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.1850903).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CNTNAP3	NM_033655.5	c.3254A>G	p.His1085Arg	missense_variant	Exon 20 of 24	ENST00000297668.11	NP_387504.2
CNTNAP3	NM_001393379.1	c.3011A>G	p.His1004Arg	missense_variant	Exon 19 of 23		NP_001380308.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CNTNAP3	ENST00000297668.11	c.3254A>G	p.His1085Arg	missense_variant	Exon 20 of 24	1	NM_033655.5	ENSP00000297668.6
CNTNAP3	ENST00000377656.6	c.3011A>G	p.His1004Arg	missense_variant	Exon 19 of 23	1		ENSP00000366884.2
CNTNAP3	ENST00000358144.6	c.2990A>G	p.His997Arg	missense_variant	Exon 18 of 18	5		ENSP00000350863.2
CNTNAP3	ENST00000493965.5	n.85A>G		non_coding_transcript_exon_variant	Exon 2 of 5	5

Frequencies

GnomAD3 genomes Cov.: 29

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 29

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.087
BayesDel_addAF	Uncertain	0.043	T
BayesDel_noAF	Benign	-0.18
CADD	Benign	16
DANN	Benign	0.72
DEOGEN2	Benign	0.17	T;.;.
Eigen	Benign	-0.46
Eigen_PC	Benign	-0.46
FATHMM_MKL	Benign	0.37	N
LIST_S2	Benign	0.72	T;D;T
M_CAP	Benign	0.033	D
MetaRNN	Benign	0.19	T;T;T
MetaSVM	Benign	-0.81	T
MutationAssessor	Uncertain	2.0	M;.;.
PhyloP100		2.4
PrimateAI	Uncertain	0.68	T
PROVEAN	Uncertain	-2.7	D;D;N
REVEL	Uncertain	0.45
Sift	Benign	0.33	T;T;T
Sift4G	Benign	0.38	T;T;T
Polyphen		0.21	B;P;.
Vest4		0.32
MutPred		0.55		Loss of ubiquitination at K1081 (P = 0.0481);.;.;
MVP		0.55
ClinPred		0.25	T
GERP RS		2.7
Varity_R		0.18
gMVP		0.16
Mutation Taster		=90/10	polymorphism

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

Other links and lift over

dbSNP: rs1369109182; hg19: chr9-39086813;