Variant 1-227733920-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate

The NM_023007.3(JMJD4):c.541C>A(p.Pro181Thr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000274 in 1,461,374 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000027 ( 0 hom. )

Consequence

JMJD4
NM_023007.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 8.92

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 4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.906

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
JMJD4	NM_023007.3 linkuse as main transcript	c.541C>A	p.Pro181Thr	missense_variant	3/6	ENST00000620518.5	NP_075383.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
JMJD4	ENST00000620518.5 linkuse as main transcript	c.541C>A	p.Pro181Thr	missense_variant	3/6	1	NM_023007.3	ENSP00000477669	P1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000121

AC:

AN:

248152

Hom.:

AF XY:

0.0000223

AC XY:

AN XY:

134598

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:

0.0000653

Gnomad FIN exome

AF:

0.0000464

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000274

AC:

AN:

1461374

Hom.:

Cov.:

AF XY:

0.00000550

AC XY:

AN XY:

726990

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:

0.0000232

Gnomad4 FIN exome

AF:

0.0000189

Gnomad4 NFE exome

AF:

8.99e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ExAC

AF:

0.0000165

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

Jan 19, 2022

The c.679C>A (p.P227T) alteration is located in exon 3 (coding exon 3) of the JMJD4 gene. This alteration results from a C to A substitution at nucleotide position 679, causing the proline (P) at amino acid position 227 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

Pathogenic

0.87

BayesDel_addAF

Benign

-0.000072

BayesDel_noAF

Uncertain

-0.060

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.14

T;T;T;.

Eigen

Uncertain

0.65

Eigen_PC

Uncertain

0.55

FATHMM_MKL

Uncertain

0.96

LIST_S2

Uncertain

0.94

.;D;D;D

M_CAP

Benign

0.022

MetaRNN

Pathogenic

0.91

D;D;D;D

MetaSVM

Benign

-0.87

MutationAssessor

Pathogenic

3.1

M;M;.;M

MutationTaster

Benign

1.0

D;D;D

PrimateAI

Uncertain

0.65

PROVEAN

Pathogenic

-6.5

D;.;.;.

REVEL

Uncertain

0.34

Sift

Uncertain

0.0050

D;.;.;.

Sift4G

Uncertain

0.0080

D;D;D;D

Polyphen

0.94

P;P;.;P

Vest4

0.87

MutPred

0.65

Gain of catalytic residue at P227 (P = 0.0487);Gain of catalytic residue at P227 (P = 0.0487);.;Gain of catalytic residue at P227 (P = 0.0487);

MVP

0.50

MPC

0.55

ClinPred

0.92

GERP RS

4.3

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.48

gMVP

0.82

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