chr17-76723968-G-C

Position:

• chr17-76723968-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP3

The NM_015167.3(JMJD6):​c.609C>G​(p.His203Gln) 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 1,461,888 control chromosomes in the GnomAD database, with no homozygous occurrence. 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)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: JMJD6 NM_015167.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.38

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 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.818

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
JMJD6	NM_015167.3	c.609C>G	p.His203Gln	missense_variant	3/6	ENST00000397625.9
JMJD6	NM_001081461.2	c.609C>G	p.His203Gln	missense_variant	3/7
JMJD6	XM_047435688.1	c.609C>G	p.His203Gln	missense_variant	3/6
JMJD6	XM_047435689.1	c.609C>G	p.His203Gln	missense_variant	3/6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
JMJD6	ENST00000397625.9	c.609C>G	p.His203Gln	missense_variant	3/6	1	NM_015167.3	P1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461888 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 727244

Gnomad4 AFR exome AF: 0.0000299

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: 0.00

Gnomad4 OTH exome AF: 0.00

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

Jun 17, 2024

The c.609C>G (p.H203Q) alteration is located in exon 3 (coding exon 3) of the JMJD6 gene. This alteration results from a C to G substitution at nucleotide position 609, causing the histidine (H) at amino acid position 203 to be replaced by a glutamine (Q). 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	0.59
BayesDel_addAF	Pathogenic	0.23	D
BayesDel_noAF	Uncertain	0.090
CADD	Uncertain	24
DANN	Uncertain	0.98
DEOGEN2	Benign	0.11	.;T;T;T
Eigen	Uncertain	0.27
Eigen_PC	Uncertain	0.27
FATHMM_MKL	Uncertain	0.97	D
LIST_S2	Uncertain	0.94	D;D;D;D
M_CAP	Benign	0.054	D
MetaRNN	Pathogenic	0.82	D;D;D;D
MetaSVM	Benign	-0.42	T
MutationAssessor	Uncertain	2.3	M;.;M;.
MutationTaster	Benign	1.0	D;D;D
PrimateAI	Pathogenic	0.89	D
PROVEAN	Pathogenic	-6.6	D;.;D;.
REVEL	Uncertain	0.47
Sift	Uncertain	0.017	D;.;D;.
Sift4G	Uncertain	0.030	D;D;D;D
Polyphen		0.80	P;.;P;.
Vest4		0.89
MutPred		0.48		Gain of MoRF binding (P = 0.1003);Gain of MoRF binding (P = 0.1003);Gain of MoRF binding (P = 0.1003);Gain of MoRF binding (P = 0.1003);
MVP		0.72
MPC		0.80
ClinPred		0.99	D
GERP RS		3.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.82
gMVP		0.75

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: chr17-74720050;