Variant 14-59504062-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_016475.5(JKAMP):c.926A>G(p.Asn309Ser) variant causes a missense change. The variant allele was found at a frequency of 0.00129 in 1,608,162 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00079 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0013 ( 3 hom. )

Consequence

JKAMP
NM_016475.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.14

Variant links:

Genes affected

JKAMP (HGNC:20184): (JNK1/MAPK8 associated membrane protein) Enables ubiquitin protein ligase binding activity. Involved in ubiquitin-dependent ERAD pathway. Predicted to be located in endoplasmic reticulum membrane. Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

JKAMP links:

L3HYPDH (HGNC:):

L3HYPDH links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.008720458).

BS2

High Homozygotes in GnomAdExome4 at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
JKAMP	NM_016475.5 linkuse as main transcript	c.926A>G	p.Asn309Ser	missense_variant	7/7	ENST00000616435.5	NP_057559.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
JKAMP	ENST00000616435.5 linkuse as main transcript	c.926A>G	p.Asn309Ser	missense_variant	7/7	5	NM_016475.5	ENSP00000479775	P1	Q9P055-4

Frequencies

GnomAD3 genomes

AF:

0.000788

AC:

120

AN:

152228

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000655

Gnomad ASJ

AF:

0.00403

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.0000941

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00123

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.000865

AC:

215

AN:

248646

Hom.:

AF XY:

0.000867

AC XY:

117

AN XY:

134900

show subpopulations

Gnomad AFR exome

AF:

0.000129

Gnomad AMR exome

AF:

0.000378

Gnomad ASJ exome

AF:

0.00447

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000458

Gnomad FIN exome

AF:

0.0000932

Gnomad NFE exome

AF:

0.00117

Gnomad OTH exome

AF:

0.00116

GnomAD4 exome

AF:

0.00134

AC:

1958

AN:

1455816

Hom.:

Cov.:

AF XY:

0.00134

AC XY:

970

AN XY:

724638

show subpopulations

Gnomad4 AFR exome

AF:

0.000210

Gnomad4 AMR exome

AF:

0.000403

Gnomad4 ASJ exome

AF:

0.00391

Gnomad4 EAS exome

AF:

0.000101

Gnomad4 SAS exome

AF:

0.000464

Gnomad4 FIN exome

AF:

0.0000750

Gnomad4 NFE exome

AF:

0.00154

Gnomad4 OTH exome

AF:

0.00131

GnomAD4 genome

AF:

0.000788

AC:

120

AN:

152346

Hom.:

Cov.:

AF XY:

0.000832

AC XY:

AN XY:

74502

show subpopulations

Gnomad4 AFR

AF:

0.000240

Gnomad4 AMR

AF:

0.000654

Gnomad4 ASJ

AF:

0.00403

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.0000941

Gnomad4 NFE

AF:

0.00123

Gnomad4 OTH

AF:

0.000473

Alfa

AF:

0.00140

Hom.:

Bravo

AF:

0.000839

TwinsUK

AF:

0.00135

AC:

ALSPAC

AF:

0.00234

AC:

ESP6500AA

AF:

0.000272

AC:

ESP6500EA

AF:

0.00135

AC:

ExAC

AF:

0.000795

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

EpiCase

AF:

0.00158

EpiControl

AF:

0.000889

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

Oct 21, 2021

The c.926A>G (p.N309S) alteration is located in exon 7 (coding exon 7) of the JKAMP gene. This alteration results from a A to G substitution at nucleotide position 926, causing the asparagine (N) at amino acid position 309 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

0.065

BayesDel_addAF

Benign

-0.54

BayesDel_noAF

Benign

-0.56

CADD

Benign

DANN

Uncertain

0.99

Eigen

Benign

-0.10

Eigen_PC

Benign

0.10

FATHMM_MKL

Uncertain

0.95

LIST_S2

Uncertain

0.90

D;D;D;D

M_CAP

Benign

0.0025

MetaRNN

Benign

0.0087

T;T;T;T

MetaSVM

Benign

-1.0

MutationTaster

Benign

1.0

D;D;D;D

PrimateAI

Benign

0.46

PROVEAN

Benign

-0.48

N;N;N;N

REVEL

Benign

0.12

Sift

Benign

0.18

T;T;T;T

Sift4G

Benign

0.44

T;T;T;T

Polyphen

0.0010

B;.;B;B

Vest4

0.18

MVP

0.48

MPC

0.38

ClinPred

0.033

GERP RS

5.7

Varity_R

0.065

gMVP

0.77

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