Variant 10-30026262-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_020848.4(JCAD):c.3886G>T(p.Ala1296Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000248 in 1,613,814 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000020 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000025 ( 0 hom. )

Consequence

JCAD
NM_020848.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.479

Variant links:

Genes affected

JCAD (HGNC:29283): (junctional cadherin 5 associated) This gene encodes an endothelial cell-to-cell junction protein. Naturally occurring mutations in this gene are associated with coronary artery disease, late onset alzheimer disease, and emphysema distribution. [provided by RefSeq, Mar 2017]

JCAD links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.03748414).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
JCAD	NM_020848.4 linkuse as main transcript	c.3886G>T	p.Ala1296Ser	missense_variant	3/4	ENST00000375377.2	NP_065899.1	Q9P266
JCAD	NM_001350022.2 linkuse as main transcript	c.3886G>T	p.Ala1296Ser	missense_variant	4/5		NP_001336951.1
JCAD	NM_001350001.2 linkuse as main transcript	c.3472G>T	p.Ala1158Ser	missense_variant	4/5		NP_001336930.1
JCAD	NM_001350021.2 linkuse as main transcript	c.3472G>T	p.Ala1158Ser	missense_variant	4/5		NP_001336950.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
JCAD	ENST00000375377.2 linkuse as main transcript	c.3886G>T	p.Ala1296Ser	missense_variant	3/4	5	NM_020848.4	ENSP00000364526.1		Q9P266

Frequencies

GnomAD3 genomes

AF:

0.0000197

AC:

AN:

152250

Hom.:

Cov.:

show subpopulations

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:

0.000621

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000401

AC:

AN:

249152

Hom.:

AF XY:

0.0000518

AC XY:

AN XY:

135218

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000294

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000884

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000253

AC:

AN:

1461564

Hom.:

Cov.:

AF XY:

0.0000344

AC XY:

AN XY:

727122

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:

0.000406

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

8.99e-7

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

AF:

0.0000197

AC:

AN:

152250

Hom.:

Cov.:

AF XY:

0.0000403

AC XY:

AN XY:

74380

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000621

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.00000756

ExAC

AF:

0.0000331

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

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

Sep 20, 2023

The c.3886G>T (p.A1296S) alteration is located in exon 3 (coding exon 2) of the KIAA1462 gene. This alteration results from a G to T substitution at nucleotide position 3886, causing the alanine (A) at amino acid position 1296 to be replaced by a serine (S). 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

0.083

BayesDel_addAF

Benign

-0.54

BayesDel_noAF

Benign

-0.71

CADD

Benign

0.35

DANN

Benign

0.89

DEOGEN2

Benign

0.0046

Eigen

Benign

-0.94

Eigen_PC

Benign

-0.97

FATHMM_MKL

Benign

0.26

LIST_S2

Benign

0.30

M_CAP

Benign

0.0081

MetaRNN

Benign

0.037

MetaSVM

Benign

-0.98

MutationAssessor

Benign

1.4

MutationTaster

Benign

1.0

PrimateAI

Benign

0.27

PROVEAN

Benign

-0.26

REVEL

Benign

0.073

Sift

Benign

0.37

Sift4G

Benign

0.48

Polyphen

0.56

Vest4

0.041

MutPred

0.25

Gain of phosphorylation at A1296 (P = 0.013);

MVP

0.12

MPC

0.20

ClinPred

0.039

GERP RS

3.5

Varity_R

0.018

gMVP

0.030

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

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