Variant 1-227734693-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_023007.3(JMJD4):c.386C>T(p.Ser129Phe) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000109 in 1,461,832 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.000011 ( 0 hom. )

Consequence

JMJD4
NM_023007.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 8.95

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:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
JMJD4	NM_023007.3 linkuse as main transcript	c.386C>T	p.Ser129Phe	missense_variant	2/6	ENST00000620518.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
JMJD4	ENST00000620518.5 linkuse as main transcript	c.386C>T	p.Ser129Phe	missense_variant	2/6	1	NM_023007.3	P1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000239

AC:

AN:

251340

Hom.:

AF XY:

0.0000221

AC XY:

AN XY:

135880

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000173

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000109

AC:

AN:

1461832

Hom.:

Cov.:

AF XY:

0.00000963

AC XY:

AN XY:

727216

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000157

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000464

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000450

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.0000151

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

Jun 13, 2022

The c.524C>T (p.S175F) alteration is located in exon 2 (coding exon 2) of the JMJD4 gene. This alteration results from a C to T substitution at nucleotide position 524, causing the serine (S) at amino acid position 175 to be replaced by a phenylalanine (F). 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

Uncertain

0.42

BayesDel_addAF

Benign

-0.15

BayesDel_noAF

Benign

-0.19

Cadd

Benign

Dann

Uncertain

0.99

DEOGEN2

Benign

0.066

T;T;T;.

Eigen

Uncertain

0.41

Eigen_PC

Uncertain

0.44

FATHMM_MKL

Uncertain

0.76

M_CAP

Benign

0.047

MetaRNN

Uncertain

0.70

D;D;D;D

MetaSVM

Benign

-0.69

MutationAssessor

Pathogenic

3.5

M;M;.;M

MutationTaster

Benign

1.0

D;D;D

PrimateAI

Uncertain

0.70

PROVEAN

Uncertain

-3.9

D;.;.;.

REVEL

Benign

0.26

Sift

Uncertain

0.0030

D;.;.;.

Sift4G

Uncertain

0.0070

D;D;D;D

Polyphen

0.15

B;B;.;P

Vest4

0.76

MutPred

0.48

Loss of disorder (P = 0.0877);Loss of disorder (P = 0.0877);.;Loss of disorder (P = 0.0877);

MVP

0.59

MPC

0.44

ClinPred

0.89

GERP RS

3.6

Varity_R

0.44

gMVP

0.75

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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