15-41834758-C-T

Variant names:

• chr15-41834758-C-T
• NM_001114632.2:c.83C>T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001114632.2(JMJD7):​c.83C>T​(p.Ala28Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,808 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 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. A28G) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: JMJD7 NM_001114632.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.51

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

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.06541067).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
JMJD7	NM_001114632.2	c.83C>T	p.Ala28Val	missense_variant	Exon 2 of 8	ENST00000397299.9	NP_001108104.1
JMJD7-PLA2G4B	NM_005090.4	c.83C>T	p.Ala28Val	missense_variant	Exon 2 of 25		NP_005081.1
JMJD7-PLA2G4B	NM_001198588.2	c.83C>T	p.Ala28Val	missense_variant	Exon 2 of 24		NP_001185517.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
JMJD7	ENST00000397299.9	c.83C>T	p.Ala28Val	missense_variant	Exon 2 of 8	1	NM_001114632.2	ENSP00000380467.4
JMJD7-PLA2G4B	ENST00000382448.8	c.83C>T	p.Ala28Val	missense_variant	Exon 2 of 25	2		ENSP00000371886.4

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461808 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 727190

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: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 8.99e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Benign	-0.20	T
BayesDel_noAF	Benign	-0.53
CADD	Benign	15
DANN	Uncertain	0.99
DEOGEN2	Benign	0.0094	T;.;.
Eigen	Benign	-0.74
Eigen_PC	Benign	-0.67
FATHMM_MKL	Benign	0.74	D
LIST_S2	Benign	0.64	T;T;T
M_CAP	Benign	0.017	T
MetaRNN	Benign	0.065	T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.3	L;.;.
PrimateAI	Benign	0.46	T
PROVEAN	Benign	-0.92	N;N;N
REVEL	Benign	0.068
Sift	Benign	0.20	T;T;T
Sift4G	Benign	0.31	T;T;T
Polyphen		0.0	B;.;.
Vest4		0.12
MutPred		0.28		Loss of phosphorylation at Y31 (P = 0.1826);Loss of phosphorylation at Y31 (P = 0.1826);Loss of phosphorylation at Y31 (P = 0.1826);
MVP		0.16
MPC		0.021
ClinPred		0.040	T
GERP RS		1.3
Varity_R		0.10
gMVP		0.35

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr15-42126956;