15-41834828-G-C

Variant names:

• chr15-41834828-G-C
• NM_001114632.2:c.153G>C
• JMJD7 p.Pro51Pro

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_001114632.2(JMJD7):​c.153G>C​(p.Pro51Pro) variant causes a synonymous 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. P51P) has been classified as Benign.

• Frequency: Genomes: not found (cov: 33)
• Consequence: JMJD7 NM_001114632.2 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0680
• 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]

ACMG classification

Our verdict: Likely_benign. The variant received -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.51).
• BP7: Synonymous conserved (PhyloP=0.068 with no splicing effect.

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.153G>C	p.Pro51Pro	synonymous	Exon 2 of 8	NP_001108104.1	P0C870
	JMJD7-PLA2G4B	NM_005090.4		c.153G>C	p.Pro51Pro	synonymous	Exon 2 of 25	NP_005081.1
	JMJD7-PLA2G4B	NM_001198588.2		c.153G>C	p.Pro51Pro	synonymous	Exon 2 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.153G>C	p.Pro51Pro	synonymous	Exon 2 of 8	ENSP00000380467.4	P0C870
	JMJD7-PLA2G4B	ENST00000382448.8	TSL:2	c.153G>C	p.Pro51Pro	synonymous	Exon 2 of 25	ENSP00000371886.4
	JMJD7	ENST00000431823.1	TSL:5	c.-145G>C		5_prime_UTR_premature_start_codon_gain	Exon 3 of 7	ENSP00000399600.1	C9K0I3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.51
CADD	Benign	2.6
DANN	Benign	0.75
PhyloP100		0.068

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr15-42127026;