17-76723796-G-T

Position:

• chr17-76723796-G-T

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The ENST00000397625.9(JMJD6):​c.781C>A​(p.Pro261Thr) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 31)
• Consequence: JMJD6 ENST00000397625.9 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.79

Genes affected

JMJD6 (HGNC:19355): (jumonji domain containing 6, arginine demethylase and lysine hydroxylase) This gene encodes a nuclear protein with a JmjC domain. JmjC domain-containing proteins are predicted to function as protein hydroxylases or histone demethylases. This protein was first identified as a putative phosphatidylserine receptor involved in phagocytosis of apoptotic cells; however, subsequent studies have indicated that it does not directly function in the clearance of apoptotic cells, and questioned whether it is a true phosphatidylserine receptor. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Uncertain_significance. Variant got 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.925

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
JMJD6	NM_015167.3	c.781C>A	p.Pro261Thr	missense_variant	3/6	ENST00000397625.9	NP_055982.2
JMJD6	NM_001081461.2	c.781C>A	p.Pro261Thr	missense_variant	3/7		NP_001074930.1
JMJD6	XM_047435688.1	c.781C>A	p.Pro261Thr	missense_variant	3/6		XP_047291644.1
JMJD6	XM_047435689.1	c.781C>A	p.Pro261Thr	missense_variant	3/6		XP_047291645.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
JMJD6	ENST00000397625.9	c.781C>A	p.Pro261Thr	missense_variant	3/6	1	NM_015167.3	ENSP00000380750.4

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 31

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Feb 26, 2024

The c.781C>A (p.P261T) alteration is located in exon 3 (coding exon 3) of the JMJD6 gene. This alteration results from a C to A substitution at nucleotide position 781, causing the proline (P) at amino acid position 261 to be replaced by a threonine (T). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.63
BayesDel_addAF	Pathogenic	0.42	D
BayesDel_noAF	Pathogenic	0.37
CADD	Pathogenic	28
DANN	Uncertain	1.0
DEOGEN2	Benign	0.34	.;T;D;T
Eigen	Pathogenic	0.91
Eigen_PC	Pathogenic	0.85
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Pathogenic	0.98	D;D;D;D
M_CAP	Uncertain	0.13	D
MetaRNN	Pathogenic	0.93	D;D;D;D
MetaSVM	Uncertain	0.59	D
MutationAssessor	Pathogenic	3.5	H;.;H;.
MutationTaster	Benign	1.0	D;D;D
PrimateAI	Pathogenic	0.82	D
PROVEAN	Pathogenic	-7.7	D;.;D;.
REVEL	Pathogenic	0.81
Sift	Uncertain	0.0010	D;.;D;.
Sift4G	Uncertain	0.0030	D;D;D;D
Polyphen		1.0	D;.;D;.
Vest4		0.86
MutPred		0.78		Loss of methylation at K260 (P = 0.0786);Loss of methylation at K260 (P = 0.0786);Loss of methylation at K260 (P = 0.0786);Loss of methylation at K260 (P = 0.0786);
MVP		0.73
MPC		1.6
ClinPred		1.0	D
GERP RS		5.4
Varity_R		0.79
gMVP		0.78

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: chr17-74719878;