rs200050685

Variant names:

• chr1-227733508-C-A
• rs200050685
• NM_023007.3:c.728G>T

Your query was ambiguous. Multiple possible variants found:

• chr1-227733508-C-A
• chr1-227733508-C-T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_023007.3(JMJD4):​c.728G>T​(p.Arg243Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 17/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R243W) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 33)
• Consequence: JMJD4 NM_023007.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.01
• 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.06534782).

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.728G>T	p.Arg243Leu	missense	Exon 4 of 6	NP_075383.3	Q9H9V9-3
	JMJD4	NM_001161465.2		c.728G>T	p.Arg243Leu	missense	Exon 4 of 6	NP_001154937.2	Q9H9V9-2
	SNAP47	NM_001323930.2		c.-46+4722C>A		intron	N/A	NP_001310859.1	A0A087X0B7

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	JMJD4	ENST00000620518.5	TSL:1 MANE Select	c.728G>T	p.Arg243Leu	missense	Exon 4 of 6	ENSP00000477669.1	Q9H9V9-3
	JMJD4	ENST00000857562.1		c.746G>T	p.Arg249Leu	missense	Exon 4 of 6	ENSP00000527621.1
	JMJD4	ENST00000972391.1		c.725G>T	p.Arg242Leu	missense	Exon 4 of 6	ENSP00000642450.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Benign	-0.20	T
BayesDel_noAF	Benign	-0.52
CADD	Benign	0.051
DANN	Benign	0.56
DEOGEN2	Benign	0.0062	T
Eigen	Benign	-1.9
Eigen_PC	Benign	-2.0
FATHMM_MKL	Benign	0.058	N
LIST_S2	Benign	0.47	T
M_CAP	Benign	0.014	T
MetaRNN	Benign	0.065	T
MetaSVM	Benign	-0.96	T
MutationAssessor	Benign	1.4	L
PhyloP100		-1.0
PrimateAI	Benign	0.38	T
PROVEAN	Benign	-1.3	N
REVEL	Benign	0.14
Sift	Benign	0.51	T
Sift4G	Benign	0.55	T
Polyphen		0.0020	B
Vest4		0.35
MutPred		0.47		Loss of disorder (P = 0.0683)
MVP		0.092
MPC		0.16
ClinPred		0.038	T
GERP RS		-9.0
Varity_R		0.023
gMVP		0.45
Mutation Taster		=96/4	polymorphism

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

Other links and lift over

dbSNP: rs200050685; hg19: chr1-227921209; COSMIC: COSV59918275; COSMIC: COSV59918275;