NM_023007.3:c.947C>A

Variant names:

• chr1-227732903-G-T
• NM_023007.3:c.947C>A

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_023007.3(JMJD4):​c.947C>A​(p.Pro316His) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: JMJD4 NM_023007.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.90

Genes affected

JMJD4 (HGNC:25724): (jumonji domain containing 4) Enables 2-oxoglutarate-dependent dioxygenase activity. Involved in positive regulation of translational termination and protein hydroxylation. Located in cytoplasm. [provided by Alliance of Genome Resources, Apr 2022]

SNAP47 (HGNC:30669): (synaptosome associated protein 47) Predicted to enable SNAP receptor activity and syntaxin binding activity. Predicted to be involved in synaptic vesicle fusion to presynaptic active zone membrane and synaptic vesicle priming. Predicted to act upstream of or within long-term synaptic potentiation. Colocalizes with BLOC-1 complex. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.2751686).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
JMJD4	NM_023007.3	c.947C>A	p.Pro316His	missense_variant	Exon 5 of 6	ENST00000620518.5	NP_075383.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
JMJD4	ENST00000620518.5	c.947C>A	p.Pro316His	missense_variant	Exon 5 of 6	1	NM_023007.3	ENSP00000477669.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 34

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Apr 22, 2022

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.1085C>A (p.P362H) alteration is located in exon 5 (coding exon 5) of the JMJD4 gene. This alteration results from a C to A substitution at nucleotide position 1085, causing the proline (P) at amino acid position 362 to be replaced by a histidine (H). 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	Benign	0.21
BayesDel_addAF	Benign	-0.030	T
BayesDel_noAF	Benign	-0.28
CADD	Benign	22
DANN	Uncertain	0.99
DEOGEN2	Benign	0.0042	T;T;T
Eigen	Benign	-0.026
Eigen_PC	Benign	0.0027
FATHMM_MKL	Benign	0.65	D
LIST_S2	Uncertain	0.87	.;D;D
M_CAP	Benign	0.032	D
MetaRNN	Benign	0.28	T;T;T
MetaSVM	Benign	-0.66	T
MutationAssessor	Uncertain	2.5	M;M;.
PrimateAI	Benign	0.47	T
PROVEAN	Benign	-1.4	N;.;.
REVEL	Benign	0.12
Sift	Benign	0.039	D;.;.
Sift4G	Benign	0.073	T;T;D
Polyphen		0.32	B;B;.
Vest4		0.42
MutPred		0.40		Loss of helix (P = 0.0558);Loss of helix (P = 0.0558);.;
MVP		0.65
MPC		0.16
ClinPred		0.69	D
GERP RS		2.8
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.081
gMVP		0.27

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: chr1-227920604;