9-41894003-T-C

Position:

• chr9-41894003-T-C

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BP4_Strong

The NM_001201380.3(CNTNAP3B):​c.3853A>G​(p.Lys1285Glu) 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: 𝑓 0.0041 (0 hom., cov: 1)
  • Exomes 𝑓: 0.0076 (6 hom.)
  • Failed GnomAD Quality Control
• Consequence: CNTNAP3B NM_001201380.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.361

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 -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.012703717).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CNTNAP3B	NM_001201380.3	c.3853A>G	p.Lys1285Glu	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.3853A>G	p.Lys1285Glu	missense_variant	24/24	1	NM_001201380.3	ENSP00000478671.2

Frequencies

GnomAD3 genomes AF: 0.00 AC: 14 AN: 3454 Hom.: 0 Cov.: 1 FAILED QC

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00284

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00282

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00791

Gnomad OTH AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00763 AC: 1052 AN: 137876 Hom.: 6 Cov.: 0 AF XY: 0.00689 AC XY: 515 AN XY: 74740

Gnomad4 AFR exome AF: 0.00161

Gnomad4 AMR exome AF: 0.00627

Gnomad4 ASJ exome AF: 0.00250

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00334

Gnomad4 FIN exome AF: 0.00474

Gnomad4 NFE exome AF: 0.0109

Gnomad4 OTH exome AF: 0.00703

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.00405 AC: 14 AN: 3456 Hom.: 0 Cov.: 1 AF XY: 0.00527 AC XY: 9 AN XY: 1708

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.00284

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00282

Gnomad4 NFE AF: 0.00793

Gnomad4 OTH AF: 0.00

Alfa AF: 0.00531 Hom.: 0

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

Dec 28, 2023

The c.3853A>G (p.K1285E) alteration is located in exon 24 (coding exon 24) of the CNTNAP3B gene. This alteration results from a A to G substitution at nucleotide position 3853, causing the lysine (K) at amino acid position 1285 to be replaced by a glutamic acid (E). 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	0.058
BayesDel_noAF	Benign	-0.65
CADD	Benign	7.7
DANN	Benign	0.57
DEOGEN2	Benign	0.00023	.;T
LIST_S2	Benign	0.34	T;T
MetaRNN	Benign	0.013	T;T
Sift4G	Benign	0.22	T;T
Vest4		0.13
gMVP		0.16

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs1184660811; hg19: chr9-65661958;