9-41893993-C-A

Position:

• chr9-41893993-C-A

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_001201380.3(CNTNAP3B):​c.3863G>T​(p.Cys1288Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 6/7 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 1)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: CNTNAP3B NM_001201380.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.59

Genes affected

CNTNAP3B (HGNC:32035): (contactin associated protein family member 3B) Predicted to be involved in cell adhesion. Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.13838288).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CNTNAP3B	NM_001201380.3	c.3863G>T	p.Cys1288Phe	missense_variant	24/24	ENST00000377561.7	NP_001188309.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CNTNAP3B	ENST00000377561.7	c.3863G>T	p.Cys1288Phe	missense_variant	24/24	1	NM_001201380.3	ENSP00000478671.2

Frequencies

GnomAD3 genomes Cov.: 1

GnomAD4 exome Data not reliable, filtered out with message: AC0;AS_VQSR AF: 0.00 AC: 0 AN: 146826 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 79546

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: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 1

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Nov 08, 2022

The c.3863G>T (p.C1288F) alteration is located in exon 24 (coding exon 24) of the CNTNAP3B gene. This alteration results from a G to T substitution at nucleotide position 3863, causing the cysteine (C) at amino acid position 1288 to be replaced by a phenylalanine (F). 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	Benign	0.066
BayesDel_noAF	Benign	-0.56
CADD	Benign	21
DANN	Benign	0.61
DEOGEN2	Benign	0.0035	.;T
LIST_S2	Benign	0.51	T;T
MetaRNN	Benign	0.14	T;T
Sift4G	Pathogenic	0.0	D;D
Vest4		0.27
gMVP		0.12

Splicing

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: chr9-65661968;