Variant 9-41893994-A-G details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_001201380.3(CNTNAP3B):c.3862T>C(p.Cys1288Arg) 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 (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. C1288F) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.0 ( 0 hom., cov: 1)

Exomes 𝑓: 0.0000069 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

CNTNAP3B
NM_001201380.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.60

Variant links:

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]

CNTNAP3B links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.12676948).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CNTNAP3B	NM_001201380.3 linkuse as main transcript	c.3862T>C	p.Cys1288Arg	missense_variant	24/24	ENST00000377561.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CNTNAP3B	ENST00000377561.7 linkuse as main transcript	c.3862T>C	p.Cys1288Arg	missense_variant	24/24	1	NM_001201380.3	P1	Q96NU0-1
CNTNAP3B	ENST00000612828.4 linkuse as main transcript	c.3619T>C	p.Cys1207Arg	missense_variant	23/23	1
CNTNAP3B	ENST00000476961.5 linkuse as main transcript	c.538T>C	p.Cys180Arg	missense_variant	5/5	1
CNTNAP3B	ENST00000619138.4 linkuse as main transcript	c.*626T>C		3_prime_UTR_variant, NMD_transcript_variant	22/22	1

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

AN:

3280

Hom.:

Cov.:

FAILED QC

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.00000687

AC:

AN:

145464

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

78824

show subpopulations

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:

0.000136

GnomAD4 genome

Data not reliable, filtered out with message: AC0;AS_VQSR

AF:

0.00

AC:

AN:

3280

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

1604

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Feb 13, 2024

The c.3862T>C (p.C1288R) alteration is located in exon 24 (coding exon 24) of the CNTNAP3B gene. This alteration results from a T to C substitution at nucleotide position 3862, causing the cysteine (C) at amino acid position 1288 to be replaced by an arginine (R). 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

0.091

BayesDel_noAF

Benign

-0.61

CADD

Benign

DANN

Benign

0.42

DEOGEN2

Benign

0.0016

.;T

LIST_S2

Benign

0.44

T;T

MetaRNN

Benign

0.13

T;T

Sift4G

Pathogenic

0.0

D;D

Vest4

0.23

gMVP

0.13

Splicing

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over