Variant 1-227732967-G-A details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_023007.3(JMJD4):c.883C>T(p.Arg295Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00057 in 1,613,354 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/23 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00040 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00059 ( 2 hom. )

Consequence

JMJD4
NM_023007.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.01

Variant links:

Genes affected

JMJD4 (HGNC:25724): (jumonji domain containing 4) Enables 2-oxoglutarate-dependent dioxygenase activity. Involved in positive regulation of translational termination and protein hydroxylation. Located in cytoplasm. [provided by Alliance of Genome Resources, Apr 2022]

JMJD4 links:

SNAP47 (HGNC:30669): (synaptosome associated protein 47) Predicted to enable SNAP receptor activity and syntaxin binding activity. Predicted to be involved in synaptic vesicle fusion to presynaptic active zone membrane and synaptic vesicle priming. Predicted to act upstream of or within long-term synaptic potentiation. Colocalizes with BLOC-1 complex. [provided by Alliance of Genome Resources, Apr 2022]

SNAP47 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
JMJD4	NM_023007.3 linkuse as main transcript	c.883C>T	p.Arg295Cys	missense_variant	5/6	ENST00000620518.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
JMJD4	ENST00000620518.5 linkuse as main transcript	c.883C>T	p.Arg295Cys	missense_variant	5/6	1	NM_023007.3	P1

Frequencies

GnomAD3 genomes

AF:

0.000401

AC:

AN:

152216

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000724

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000622

Gnomad FIN

AF:

0.000471

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000691

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.000431

AC:

108

AN:

250830

Hom.:

AF XY:

0.000376

AC XY:

AN XY:

135818

show subpopulations

Gnomad AFR exome

AF:

0.000123

Gnomad AMR exome

AF:

0.000434

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000653

Gnomad FIN exome

AF:

0.000648

Gnomad NFE exome

AF:

0.000592

Gnomad OTH exome

AF:

0.00131

GnomAD4 exome

AF:

0.000587

AC:

858

AN:

1461020

Hom.:

Cov.:

AF XY:

0.000553

AC XY:

402

AN XY:

726804

show subpopulations

Gnomad4 AFR exome

AF:

0.000119

Gnomad4 AMR exome

AF:

0.000380

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000580

Gnomad4 FIN exome

AF:

0.000551

Gnomad4 NFE exome

AF:

0.000701

Gnomad4 OTH exome

AF:

0.000381

GnomAD4 genome

AF:

0.000400

AC:

AN:

152334

Hom.:

Cov.:

AF XY:

0.000389

AC XY:

AN XY:

74478

show subpopulations

Gnomad4 AFR

AF:

0.0000721

Gnomad4 AMR

AF:

0.000131

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000622

Gnomad4 FIN

AF:

0.000471

Gnomad4 NFE

AF:

0.000691

Gnomad4 OTH

AF:

0.000473

Alfa

AF:

0.000397

Hom.:

Bravo

AF:

0.000332

TwinsUK

AF:

0.00108

AC:

ALSPAC

AF:

0.00104

AC:

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.000349

AC:

ExAC

AF:

0.000486

AC:

Asia WGS

AF:

0.000577

AC:

AN:

3478

EpiCase

AF:

0.000436

EpiControl

AF:

0.000711

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Inborn genetic diseases

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 07, 2021

The c.1021C>T (p.R341C) alteration is located in exon 5 (coding exon 5) of the JMJD4 gene. This alteration results from a C to T substitution at nucleotide position 1021, causing the arginine (R) at amino acid position 341 to be replaced by a cysteine (C). 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

0.090

BayesDel_addAF

Benign

-0.41

BayesDel_noAF

Benign

-0.44

Cadd

Benign

Dann

Uncertain

0.98

DEOGEN2

Benign

0.086

T;T;T;.

Eigen

Benign

-0.46

Eigen_PC

Benign

-0.30

FATHMM_MKL

Uncertain

0.82

M_CAP

Benign

0.033

MetaRNN

Benign

0.033

T;T;T;T

MetaSVM

Benign

-0.90

MutationAssessor

Benign

1.6

L;L;.;L

MutationTaster

Benign

1.0

D;D;D

PrimateAI

Benign

0.31

PROVEAN

Uncertain

-2.9

D;.;.;.

REVEL

Benign

0.11

Sift

Benign

0.18

T;.;.;.

Sift4G

Benign

0.11

T;T;T;T

Polyphen

0.0020

B;B;.;B

Vest4

0.25

MVP

0.49

MPC

0.17

ClinPred

0.035

GERP RS

3.0

Varity_R

0.080

gMVP

0.27

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.21

Details are displayed if max score is > 0.2

DS_AG_spliceai

0.21

Position offset: -12

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