Variant 11-118212412-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001098526.2(JAML):c.193G>A(p.Ala65Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000889 in 1,461,618 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000089 ( 0 hom. )

Consequence

JAML
NM_001098526.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.301

Variant links:

Genes affected

JAML (HGNC:19084): (junction adhesion molecule like) Enables integrin binding activity and protein homodimerization activity. Involved in heterophilic cell-cell adhesion via plasma membrane cell adhesion molecules and myeloid leukocyte migration. Located in bicellular tight junction; nucleoplasm; and plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

JAML links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.11166027).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
JAML	NM_001098526.2 linkuse as main transcript	c.193G>A	p.Ala65Thr	missense_variant	3/10	ENST00000356289.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
JAML	ENST00000356289.10 linkuse as main transcript	c.193G>A	p.Ala65Thr	missense_variant	3/10	1	NM_001098526.2	P2	Q86YT9-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000159

AC:

AN:

250990

Hom.:

AF XY:

0.0000147

AC XY:

AN XY:

135650

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000868

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000327

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000889

AC:

AN:

1461618

Hom.:

Cov.:

AF XY:

0.00000963

AC XY:

AN XY:

727110

show subpopulations

Gnomad4 AFR exome

AF:

0.0000597

Gnomad4 AMR exome

AF:

0.0000671

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000348

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000270

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

Cov.:

ExAC

AF:

0.00000824

AC:

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

Jul 06, 2021

The c.193G>A (p.A65T) alteration is located in exon 3 (coding exon 2) of the JAML gene. This alteration results from a G to A substitution at nucleotide position 193, causing the alanine (A) at amino acid position 65 to be replaced by a threonine (T). 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

0.077

BayesDel_addAF

Benign

-0.25

BayesDel_noAF

Benign

-0.41

CADD

Benign

DANN

Benign

0.72

DEOGEN2

Benign

0.0091

T;.;T;.;.;.;T

Eigen

Benign

-0.44

Eigen_PC

Benign

-0.61

FATHMM_MKL

Benign

0.21

LIST_S2

Benign

0.73

T;T;T;T;T;T;T

M_CAP

Benign

0.016

MetaRNN

Benign

0.11

T;T;T;T;T;T;T

MetaSVM

Benign

-0.91

MutationTaster

Benign

1.0

N;N;N;N

PrimateAI

Benign

0.26

PROVEAN

Benign

-1.5

N;N;N;N;.;N;N

REVEL

Benign

0.15

Sift

Benign

0.15

T;T;T;T;.;T;T

Sift4G

Benign

0.46

T;T;T;T;.;.;T

Polyphen

0.96

D;P;D;.;.;.;.

Vest4

0.059

MutPred

0.31

Gain of phosphorylation at A65 (P = 0.0869);.;Gain of phosphorylation at A65 (P = 0.0869);.;.;.;Gain of phosphorylation at A65 (P = 0.0869);

MVP

0.58

MPC

0.16

ClinPred

0.21

GERP RS

2.0

Varity_R

0.083

gMVP

0.15

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