NM_001114632.2:c.34G>C

Variant names:

• chr15-41828158-G-C
• rs747285917
• NM_001114632.2:c.34G>C

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001114632.2(JMJD7):​c.34G>C​(p.Glu12Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000598 in 1,337,474 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000060 (0 hom.)
• Consequence: JMJD7 NM_001114632.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.322
• Publications: 0 publications found

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-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]

ENSG00000250379 (HGNC:):

ACMG classification

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=0.07424715).

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	JMJD7	NM_001114632.2	MANE Select	c.34G>C	p.Glu12Gln	missense	Exon 1 of 8	NP_001108104.1	P0C870
	JMJD7-PLA2G4B	NM_005090.4		c.34G>C	p.Glu12Gln	missense	Exon 1 of 25	NP_005081.1
	JMJD7-PLA2G4B	NM_001198588.2		c.34G>C	p.Glu12Gln	missense	Exon 1 of 24	NP_001185517.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	JMJD7	ENST00000397299.9	TSL:1 MANE Select	c.34G>C	p.Glu12Gln	missense	Exon 1 of 8	ENSP00000380467.4	P0C870
	JMJD7-PLA2G4B	ENST00000382448.8	TSL:2	c.34G>C	p.Glu12Gln	missense	Exon 1 of 25	ENSP00000371886.4
	JMJD7-PLA2G4B	ENST00000342159.6	TSL:2	c.34G>C	p.Glu12Gln	missense	Exon 1 of 24	ENSP00000342785.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.0000335 AC: 5 AN: 149224 AF XY: 0.0000354

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: 0.0000656

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000598 AC: 8 AN: 1337474 Hom.: 0 Cov.: 31 AF XY: 0.00000606 AC XY: 4 AN XY: 659974

African (AFR) AF: 0.00 AC: 0 AN: 25994

American (AMR) AF: 0.00 AC: 0 AN: 19532

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 22316

East Asian (EAS) AF: 0.00 AC: 0 AN: 31344

South Asian (SAS) AF: 0.00 AC: 0 AN: 68168

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 50782

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4568

European-Non Finnish (NFE) AF: 0.00000660 AC: 7 AN: 1060014

Other (OTH) AF: 0.0000183 AC: 1 AN: 54756

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

ExAC AF: 0.0000497 AC: 6

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.41	T
BayesDel_noAF	Benign	-0.64
CADD	Benign	15
DANN	Uncertain	0.99
DEOGEN2	Benign	0.024	T
Eigen	Benign	-0.61
Eigen_PC	Benign	-0.61
FATHMM_MKL	Benign	0.16	N
LIST_S2	Benign	0.64	T
M_CAP	Benign	0.015	T
MetaRNN	Benign	0.074	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.4	L
PhyloP100		0.32
PrimateAI	Uncertain	0.51	T
PROVEAN	Benign	-0.50	N
REVEL	Benign	0.011
Sift	Benign	0.50	T
Sift4G	Benign	0.58	T
Polyphen		0.29	B
Vest4		0.25
MutPred		0.27		Loss of disorder (P = 0.066)
MVP		0.055
MPC		0.021
ClinPred		0.13	T
GERP RS		0.27
PromoterAI		-0.053	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.12
gMVP		0.52
Mutation Taster		=91/9	polymorphism

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

Other links and lift over

dbSNP: rs747285917; hg19: chr15-42120356; COSMIC: COSV106091037; COSMIC: COSV106091037;