rs202146888

Variant names:

• chr1-227732922-C-A
• rs202146888
• NM_023007.3:c.928G>T

Your query was ambiguous. Multiple possible variants found:

• chr1-227732922-C-A
• chr1-227732922-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_023007.3(JMJD4):​c.928G>T​(p.Glu310*) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,460,698 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: JMJD4 NM_023007.3 stop_gained
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.72
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_023007.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	JMJD4	NM_023007.3	MANE Select	c.928G>T	p.Glu310*	stop_gained	Exon 5 of 6	NP_075383.3	Q9H9V9-3
	SNAP47	NM_001323930.2		c.-46+4136C>A		intron	N/A	NP_001310859.1	A0A087X0B7
	SNAP47	NM_001323932.2		c.-46+1175C>A		intron	N/A	NP_001310861.1	A0A087X0B7

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	JMJD4	ENST00000620518.5	TSL:1 MANE Select	c.928G>T	p.Glu310*	stop_gained	Exon 5 of 6	ENSP00000477669.1	Q9H9V9-3
	JMJD4	ENST00000857562.1		c.946G>T	p.Glu316*	stop_gained	Exon 5 of 6	ENSP00000527621.1
	JMJD4	ENST00000972391.1		c.925G>T	p.Glu309*	stop_gained	Exon 5 of 6	ENSP00000642450.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.85e-7 AC: 1 AN: 1460698 Hom.: 0 Cov.: 34 AF XY: 0.00000138 AC XY: 1 AN XY: 726664

African (AFR) AF: 0.00 AC: 0 AN: 33478

American (AMR) AF: 0.00 AC: 0 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86252

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52344

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5708

European-Non Finnish (NFE) AF: 8.99e-7 AC: 1 AN: 1111984

Other (OTH) AF: 0.00 AC: 0 AN: 60376

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Pathogenic	0.40	D
BayesDel_noAF	Pathogenic	0.34
CADD	Pathogenic	36
DANN	Uncertain	0.99
Eigen	Uncertain	0.19
Eigen_PC	Benign	-0.13
FATHMM_MKL	Uncertain	0.83	D
PhyloP100		1.7
Vest4		0.29
GERP RS		0.54
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=25/175	disease causing

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.19		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs202146888; hg19: chr1-227920623;