Genetic Variant NM_023007.3:c.814C>T (chr1-227733422-G-A) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_023007.3(JMJD4):c.814C>T(p.His272Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000127 in 1,577,334 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000026 ( 0 hom., cov: 33)

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: 2.44

Publications

0 publications found

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 was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.1470207).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_023007.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
JMJD4	NM_023007.3	MANE Select	c.814C>T	p.His272Tyr	missense	Exon 4 of 6	NP_075383.3	Q9H9V9-3
JMJD4	NM_001161465.2		c.814C>T	p.His272Tyr	missense	Exon 4 of 6	NP_001154937.2	Q9H9V9-2
SNAP47	NM_001323930.2		c.-46+4636G>A		intron	N/A	NP_001310859.1	A0A087X0B7

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
JMJD4	ENST00000620518.5	TSL:1 MANE Select	c.814C>T	p.His272Tyr	missense	Exon 4 of 6	ENSP00000477669.1	Q9H9V9-3
JMJD4	ENST00000857562.1		c.832C>T	p.His278Tyr	missense	Exon 4 of 6	ENSP00000527621.1
JMJD4	ENST00000972391.1		c.811C>T	p.His271Tyr	missense	Exon 4 of 6	ENSP00000642450.1

Frequencies

GnomAD3 genomes

AF:

0.0000263

AC:

AN:

152248

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000654

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000441

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.00000895

AC:

AN:

223500

AF XY:

0.0000164

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 FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000112

AC:

AN:

1425086

Hom.:

Cov.:

AF XY:

0.0000184

AC XY:

AN XY:

705850

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

31838

American (AMR)

AF:

0.00

AC:

AN:

37228

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

24330

East Asian (EAS)

AF:

0.00

AC:

AN:

39208

South Asian (SAS)

AF:

0.0000852

AC:

AN:

82112

European-Finnish (FIN)

AF:

0.00

AC:

AN:

51560

Middle Eastern (MID)

AF:

0.000361

AC:

AN:

5544

European-Non Finnish (NFE)

AF:

0.00000457

AC:

AN:

1094544

Other (OTH)

AF:

0.0000341

AC:

AN:

58722

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0000263

AC:

AN:

152248

Hom.:

Cov.:

AF XY:

0.0000538

AC XY:

AN XY:

74390

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41468

American (AMR)

AF:

0.0000654

AC:

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5194

South Asian (SAS)

AF:

0.00

AC:

AN:

4836

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10632

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.0000441

AC:

AN:

68034

Other (OTH)

AF:

0.00

AC:

AN:

2094

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.538

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.0000264

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.0000165

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.076

BayesDel_addAF

Benign

-0.27

BayesDel_noAF

Benign

-0.63

CADD

Benign

(source)

DANN

Benign

0.83

DEOGEN2

Benign

0.0036

Eigen

Benign

-0.59

Eigen_PC

Benign

-0.39

FATHMM_MKL

Benign

0.66

LIST_S2

Benign

0.84

M_CAP

Benign

0.0018

MetaRNN

Benign

0.15

MetaSVM

Benign

-0.98

MutationAssessor

Benign

0.040

PhyloP100

2.4

PrimateAI

Uncertain

0.59

PROVEAN

Benign

1.8

REVEL

Benign

0.057

Sift

Benign

1.0

Sift4G

Benign

1.0

Polyphen

0.0040

Vest4

0.25

MVP

0.040

MPC

0.15

ClinPred

0.027

GERP RS

2.2

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.051

gMVP

0.54

Mutation Taster

=88/12

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over