rs1016740515

Variant names:

• chr16-76489698-C-A
• NM_033401.5:c.1895C>A

Your query was ambiguous. Multiple possible variants found:

• chr16-76489698-C-A
• chr16-76489698-C-T

Variant summary

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

The NM_033401.5(CNTNAP4):​c.1895C>A​(p.Thr632Asn) variant causes a missense change. The variant allele was found at a frequency of 0.000000697 in 1,434,840 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. T632I) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 7.0e-7 (0 hom.)
• Consequence: CNTNAP4 NM_033401.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.67

Genes affected

CNTNAP4 (HGNC:18747): (contactin associated protein family member 4) This gene encodes a member of the neurexin protein family. Members of this family function in the vertebrate nervous system as cell adhesion molecules and receptors. This protein contains epidermal growth factor repeats and laminin G domains. In addition, it includes an F5/8 type C domain, discoidin/neuropilin- and fibrinogen-like domains, and thrombospondin N-terminal-like domains. This protein may also play a role in proper neurotransmission in the dopaminergic and GABAergic systems and mutations in this gene may be associated with certain psychiatric illnesses. A polymorphism in an intron of this gene may be associated with longevity. [provided by RefSeq, Apr 2016]

ENSG00000287694 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CNTNAP4	NM_033401.5	c.1895C>A	p.Thr632Asn	missense_variant	Exon 13 of 24	ENST00000611870.5	NP_207837.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CNTNAP4	ENST00000611870.5	c.1895C>A	p.Thr632Asn	missense_variant	Exon 13 of 24	1	NM_033401.5	ENSP00000479811.1
ENSG00000287694	ENST00000655556.1	n.1895C>A		non_coding_transcript_exon_variant	Exon 13 of 25			ENSP00000499374.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.97e-7 AC: 1 AN: 1434840 Hom.: 0 Cov.: 30 AF XY: 0.00000141 AC XY: 1 AN XY: 711078

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: 9.14e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Benign	-0.11	T
BayesDel_noAF	Benign	-0.39
CADD	Pathogenic	26
DANN	Uncertain	0.99
DEOGEN2	Benign	0.36	T;T;T;.;.;.
Eigen	Uncertain	0.42
Eigen_PC	Uncertain	0.41
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.93	D;D;D;D;D;D
M_CAP	Benign	0.020	T
MetaRNN	Uncertain	0.64	D;D;D;D;D;D
MetaSVM	Benign	-0.58	T
PrimateAI	Uncertain	0.53	T
PROVEAN	Uncertain	-3.6	.;.;.;.;D;D
REVEL	Benign	0.15
Sift	Uncertain	0.010	.;.;.;.;D;D
Sift4G	Uncertain	0.0050	D;D;D;D;D;D
Polyphen		0.97	D;.;.;.;.;P
Vest4		0.61
MutPred		0.39		.;.;.;.;.;Gain of MoRF binding (P = 0.4072);
MVP		0.55
MPC		0.11
ClinPred		0.97	D
GERP RS		3.6
Varity_R		0.14
gMVP		0.63

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr16-76523595;