rs899904885

Variant names:

• chr7-27895354-A-G
• rs899904885
• NM_175061.4:c.251T>C

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_175061.4(JAZF1):​c.251T>C​(p.Leu84Pro) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000124 in 1,606,986 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 31)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: JAZF1 NM_175061.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 8.95
• Publications: 0 publications found

Genes affected

JAZF1 (HGNC:28917): (JAZF zinc finger 1) This gene encodes a nuclear protein with three C2H2-type zinc fingers, and functions as a transcriptional repressor. Chromosomal aberrations involving this gene are associated with endometrial stromal tumors. Alternatively spliced variants which encode different protein isoforms have been described; however, not all variants have been fully characterized [provided by RefSeq, Jul 2008]

JAZF1 Gene-Disease associations (from GenCC):

• systemic lupus erythematosus

  Inheritance: Unknown Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.4219123).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_175061.4. 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
	JAZF1	NM_175061.4	MANE Select	c.251T>C	p.Leu84Pro	missense	Exon 3 of 5	NP_778231.2	Q86VZ6-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	JAZF1	ENST00000283928.10	TSL:1 MANE Select	c.251T>C	p.Leu84Pro	missense	Exon 3 of 5	ENSP00000283928.5	Q86VZ6-1
	JAZF1	ENST00000427814.5	TSL:1	c.209T>C	p.Leu70Pro	missense	Exon 2 of 4	ENSP00000388302.1	H0Y403
	JAZF1	ENST00000900291.1		c.251T>C	p.Leu84Pro	missense	Exon 3 of 6	ENSP00000570350.1

Frequencies

GnomAD3 genomes AF: 0.00000663 AC: 1 AN: 150900 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000663

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 6.87e-7 AC: 1 AN: 1456086 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 724260

African (AFR) AF: 0.00 AC: 0 AN: 33256

American (AMR) AF: 0.0000228 AC: 1 AN: 43850

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26062

East Asian (EAS) AF: 0.00 AC: 0 AN: 39146

South Asian (SAS) AF: 0.00 AC: 0 AN: 85172

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53358

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5764

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1109304

Other (OTH) AF: 0.00 AC: 0 AN: 60174

GnomAD4 genome AF: 0.00000663 AC: 1 AN: 150900 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 73584

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 40964

American (AMR) AF: 0.0000663 AC: 1 AN: 15094

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3460

East Asian (EAS) AF: 0.00 AC: 0 AN: 5132

South Asian (SAS) AF: 0.00 AC: 0 AN: 4724

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10438

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67804

Other (OTH) AF: 0.00 AC: 0 AN: 2058

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.00 Hom.: 0

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.24
BayesDel_addAF	Pathogenic	0.20	D
BayesDel_noAF	Uncertain	0.040
CADD	Uncertain	26
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.075	T
Eigen	Uncertain	0.42
Eigen_PC	Uncertain	0.51
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.87	D
M_CAP	Benign	0.077	D
MetaRNN	Benign	0.42	T
MetaSVM	Benign	-0.76	T
MutationAssessor	Benign	1.9	L
PhyloP100		8.9
PrimateAI	Pathogenic	0.79	T
PROVEAN	Benign	-0.94	N
REVEL	Uncertain	0.49
Sift	Benign	0.30	T
Sift4G	Benign	0.11	T
Polyphen		1.0	D
Vest4		0.75
MutPred		0.43		Gain of relative solvent accessibility (P = 0.0098)
MVP		0.44
MPC		1.8
ClinPred		0.70	D
GERP RS		5.5
Varity_R		0.38
gMVP		0.70
Mutation Taster		=12/88	disease causing

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: rs899904885; hg19: chr7-27934973;