Variant 15-41837130-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001114632.2(JMJD7):c.925C>G(p.Leu309Val) variant causes a missense change. The variant allele was found at a frequency of 0.000000685 in 1,460,568 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

JMJD7
NM_001114632.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.76

Variant links:

Genes affected

JMJD7 (HGNC:34397): (jumonji domain containing 7) This gene encodes a highly conserved protein with a JmjC domain, which are part of the cupin metalloenzyme superfamily. JmjC proteins may function as 2-oxoglutarate-Fe(II)-dependent dioxygenases. Most tissues also express read-through transcripts from this gene into the downstream phospholipase A2, group IVB (cytosolic) gene, some of which may encode fusion proteins combining the N-terminus of this protein with the phospholipase A2, group IVB protein. [provided by RefSeq, Jul 2008]

JMJD7 links:

JMJD7-PLA2G4B (HGNC:):

JMJD7-PLA2G4B links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.210839).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
JMJD7	NM_001114632.2 linkuse as main transcript	c.925C>G	p.Leu309Val	missense_variant	8/8	ENST00000397299.9
JMJD7-PLA2G4B	NM_005090.4 linkuse as main transcript	c.702+579C>G		intron_variant
JMJD7-PLA2G4B	NM_001198588.2 linkuse as main transcript	c.702+579C>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
JMJD7	ENST00000397299.9 linkuse as main transcript	c.925C>G	p.Leu309Val	missense_variant	8/8	1	NM_001114632.2	P1
JMJD7	ENST00000408047.5 linkuse as main transcript	c.628C>G	p.Leu210Val	missense_variant	7/7	5
JMJD7	ENST00000478178.1 linkuse as main transcript	n.494C>G		non_coding_transcript_exon_variant	4/4	2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.85e-7

AC:

AN:

1460568

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

726482

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:

0.0000116

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

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

Sep 28, 2022

The c.925C>G (p.L309V) alteration is located in exon 8 (coding exon 8) of the JMJD7 gene. This alteration results from a C to G substitution at nucleotide position 925, causing the leucine (L) at amino acid position 309 to be replaced by a valine (V). 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

0.16

BayesDel_addAF

Benign

-0.092

BayesDel_noAF

Benign

-0.37

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.0094

T;T

Eigen

Benign

0.18

Eigen_PC

Uncertain

0.30

FATHMM_MKL

Uncertain

0.95

LIST_S2

Benign

0.78

T;T

M_CAP

Benign

0.032

MetaRNN

Benign

0.21

T;T

MetaSVM

Benign

-0.75

MutationAssessor

Benign

1.7

L;.

MutationTaster

Benign

0.80

D;D;D;D;N

PROVEAN

Benign

-1.3

N;N

REVEL

Benign

0.066

Sift

Benign

0.034

D;D

Sift4G

Uncertain

0.039

D;D

Polyphen

0.44

B;.

Vest4

0.21

MutPred

0.42

Gain of helix (P = 0.0022);.;

MVP

0.33

MPC

0.058

ClinPred

0.82

GERP RS

5.5

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.26

gMVP

0.55

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.070

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over