rs146955165

Variant names:

• chr15-41835004-G-A
• rs146955165
• NM_001114632.2:c.253G>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001114632.2(JMJD7):​c.253G>A​(p.Val85Met) variant causes a missense change. The variant allele was found at a frequency of 0.000209 in 1,614,090 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00027 (0 hom., cov: 33)
  • Exomes 𝑓: 0.00020 (0 hom.)
• Consequence: JMJD7 NM_001114632.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.75
• Publications: 3 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 -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.01714918).

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.253G>A	p.Val85Met	missense	Exon 3 of 8	NP_001108104.1	P0C870
	JMJD7-PLA2G4B	NM_005090.4		c.253G>A	p.Val85Met	missense	Exon 3 of 25	NP_005081.1
	JMJD7-PLA2G4B	NM_001198588.2		c.253G>A	p.Val85Met	missense	Exon 3 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.253G>A	p.Val85Met	missense	Exon 3 of 8	ENSP00000380467.4	P0C870
	JMJD7-PLA2G4B	ENST00000382448.8	TSL:2	c.253G>A	p.Val85Met	missense	Exon 3 of 25	ENSP00000371886.4
	JMJD7	ENST00000408047.5	TSL:5	c.-45G>A		5_prime_UTR_premature_start_codon_gain	Exon 2 of 7	ENSP00000384174.1	B5MC20

Frequencies

GnomAD3 genomes AF: 0.000269 AC: 41 AN: 152224 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.0000482

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00950

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000882

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000358 AC: 89 AN: 248806 AF XY: 0.000282

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00765

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000900

Gnomad OTH exome AF: 0.000327

GnomAD4 exome AF: 0.000202 AC: 296 AN: 1461748 Hom.: 0 Cov.: 31 AF XY: 0.000186 AC XY: 135 AN XY: 727182

African (AFR) AF: 0.0000597 AC: 2 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00704 AC: 184 AN: 26136

East Asian (EAS) AF: 0.0000504 AC: 2 AN: 39700

South Asian (SAS) AF: 0.0000116 AC: 1 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53278

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.0000629 AC: 70 AN: 1112008

Other (OTH) AF: 0.000613 AC: 37 AN: 60396

GnomAD4 genome AF: 0.000269 AC: 41 AN: 152342 Hom.: 0 Cov.: 33 AF XY: 0.000255 AC XY: 19 AN XY: 74488

African (AFR) AF: 0.0000481 AC: 2 AN: 41576

American (AMR) AF: 0.00 AC: 0 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.00950 AC: 33 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5184

South Asian (SAS) AF: 0.00 AC: 0 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10618

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000882 AC: 6 AN: 68038

Other (OTH) AF: 0.00 AC: 0 AN: 2114

Alfa AF: 0.000370 Hom.: 0

Bravo AF: 0.000306

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000581 AC: 5

ExAC AF: 0.000296 AC: 36

EpiCase AF: 0.000218

EpiControl AF: 0.000119

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	0.29
BayesDel_addAF	Uncertain	0.089	D
BayesDel_noAF	Uncertain	0.070
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.012	T
Eigen	Uncertain	0.67
Eigen_PC	Uncertain	0.56
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Uncertain	0.97	D
M_CAP	Uncertain	0.087	D
MetaRNN	Benign	0.017	T
MetaSVM	Uncertain	0.28	D
MutationAssessor	Pathogenic	3.2	M
PhyloP100		6.8
PrimateAI	Uncertain	0.62	T
PROVEAN	Benign	-2.2	N
REVEL	Uncertain	0.54
Sift	Uncertain	0.0030	D
Sift4G	Uncertain	0.010	D
Polyphen		1.0	D
Vest4		0.74
MVP		0.69
MPC		0.18
ClinPred		0.22	T
GERP RS		4.8
Varity_R		0.16
gMVP		0.70
Mutation Taster		=33/67	disease causing

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: rs146955165; hg19: chr15-42127202;