17-76725654-T-C

Position:

• chr17-76725654-T-C

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_015167.3(JMJD6):​c.331A>G​(p.Lys111Glu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: JMJD6 NM_015167.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 8.01

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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
JMJD6	NM_015167.3	c.331A>G	p.Lys111Glu	missense_variant	2/6	ENST00000397625.9
JMJD6	NM_001081461.2	c.331A>G	p.Lys111Glu	missense_variant	2/7
JMJD6	XM_047435688.1	c.331A>G	p.Lys111Glu	missense_variant	2/6
JMJD6	XM_047435689.1	c.331A>G	p.Lys111Glu	missense_variant	2/6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
JMJD6	ENST00000397625.9	c.331A>G	p.Lys111Glu	missense_variant	2/6	1	NM_015167.3	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 38

GnomAD4 genome Cov.: 32

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

Jun 21, 2023

The c.331A>G (p.K111E) alteration is located in exon 2 (coding exon 2) of the JMJD6 gene. This alteration results from a A to G substitution at nucleotide position 331, causing the lysine (K) at amino acid position 111 to be replaced by a glutamic acid (E). 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	1.0
BayesDel_addAF	Pathogenic	0.31	D
BayesDel_noAF	Pathogenic	0.21
CADD	Pathogenic	27
DANN	Uncertain	1.0
DEOGEN2	Benign	0.078	.;T;T;T
Eigen	Uncertain	0.34
Eigen_PC	Uncertain	0.45
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Pathogenic	0.99	D;D;D;D
M_CAP	Benign	0.050	D
MetaRNN	Uncertain	0.60	D;D;D;D
MetaSVM	Benign	-0.49	T
MutationAssessor	Uncertain	2.1	M;.;M;.
MutationTaster	Benign	1.0	D;D;D
PrimateAI	Pathogenic	0.92	D
PROVEAN	Uncertain	-3.5	D;.;D;.
REVEL	Uncertain	0.53
Sift	Uncertain	0.020	D;.;D;.
Sift4G	Uncertain	0.0070	D;D;D;D
Polyphen		0.62	P;.;P;.
Vest4		0.72
MutPred		0.36		Loss of ubiquitination at K111 (P = 0.0141);Loss of ubiquitination at K111 (P = 0.0141);Loss of ubiquitination at K111 (P = 0.0141);Loss of ubiquitination at K111 (P = 0.0141);
MVP		0.85
MPC		1.1
ClinPred		0.98	D
GERP RS		5.7
Varity_R		0.88
gMVP		0.71

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: chr17-74721736;