Genetic Variant JMJD7:p.Glu7Ala (chr15-41828144-A-C) – 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_001114632.2(JMJD7):c.20A>C(p.Glu7Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. E7G) has been classified as Benign.

Frequency

Genomes: not found (cov: 32)

Consequence

JMJD7
NM_001114632.2 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.01

Publications

7 publications found

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:34449): (JMJD7-PLA2G4B readthrough) This locus represents naturally-occurring readthrough transcription between the neighboring jumonji domain containing 7 (JMJD7) and phospholipase A2, group IVB (cytosolic) (PLA2G4B) genes. Readthrough transcripts encode fusion proteins that share amino acid sequence with each individual gene product, including a partial JmjC domain and downstream C2 and phospholipase A2 domains. Alternatively spliced transcript variants have been observed. [provided by RefSeq, Oct 2013]

JMJD7-PLA2G4B links:

ENSG00000250379 (HGNC:):

ENSG00000250379 links:

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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=0.09897646).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001114632.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
JMJD7	NM_001114632.2	MANE Select	c.20A>C	p.Glu7Ala	missense	Exon 1 of 8	NP_001108104.1	P0C870
JMJD7-PLA2G4B	NM_005090.4		c.20A>C	p.Glu7Ala	missense	Exon 1 of 25	NP_005081.1
JMJD7-PLA2G4B	NM_001198588.2		c.20A>C	p.Glu7Ala	missense	Exon 1 of 24	NP_001185517.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
JMJD7	ENST00000397299.9	TSL:1 MANE Select	c.20A>C	p.Glu7Ala	missense	Exon 1 of 8	ENSP00000380467.4	P0C870
JMJD7-PLA2G4B	ENST00000382448.8	TSL:2	c.20A>C	p.Glu7Ala	missense	Exon 1 of 25	ENSP00000371886.4
JMJD7-PLA2G4B	ENST00000342159.6	TSL:2	c.20A>C	p.Glu7Ala	missense	Exon 1 of 24	ENSP00000342785.4

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Cov.:

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.091

BayesDel_addAF

Benign

-0.28

BayesDel_noAF

Benign

-0.64

CADD

Benign

(source)

DANN

Benign

0.97

DEOGEN2

Benign

0.083

Eigen

Benign

-0.70

Eigen_PC

Benign

-0.72

FATHMM_MKL

Benign

0.35

LIST_S2

Benign

0.62

M_CAP

Benign

0.020

MetaRNN

Benign

0.099

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.55

PhyloP100

1.0

PrimateAI

Uncertain

0.59

PROVEAN

Benign

-1.7

REVEL

Benign

0.030

Sift

Benign

0.10

Sift4G

Uncertain

0.054

Polyphen

0.0070

Vest4

0.32

MutPred

0.24

Loss of loop (P = 0.0203)

MVP

0.040

MPC

0.022

ClinPred

0.074

GERP RS

1.3

PromoterAI

-0.015

Neutral

(source)

Varity_R

0.20

gMVP

0.62

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over