rs368409103

Variant names:

• chr7-27991969-C-A
• rs368409103
• NM_175061.4:c.128G>T

Your query was ambiguous. Multiple possible variants found:

• chr7-27991969-C-A
• chr7-27991969-C-T

Variant summary

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

The NM_175061.4(JAZF1):​c.128G>T​(p.Arg43Leu) variant causes a missense change. The variant allele was found at a frequency of 0.00000069 in 1,449,330 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. R43Q) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: JAZF1 NM_175061.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.75
• 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 2 ACMG points.

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

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.128G>T	p.Arg43Leu	missense	Exon 2 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.128G>T	p.Arg43Leu	missense	Exon 2 of 5	ENSP00000283928.5	Q86VZ6-1
	JAZF1	ENST00000427814.5	TSL:1	c.86G>T	p.Arg29Leu	missense	Exon 1 of 4	ENSP00000388302.1	H0Y403
	JAZF1	ENST00000900291.1		c.128G>T	p.Arg43Leu	missense	Exon 2 of 6	ENSP00000570350.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.90e-7 AC: 1 AN: 1449330 Hom.: 0 Cov.: 27 AF XY: 0.00000139 AC XY: 1 AN XY: 721750

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

African (AFR) AF: 0.00 AC: 0 AN: 33170

American (AMR) AF: 0.00 AC: 0 AN: 44598

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25996

East Asian (EAS) AF: 0.00 AC: 0 AN: 39546

South Asian (SAS) AF: 0.0000117 AC: 1 AN: 85678

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53324

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5736

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1101314

Other (OTH) AF: 0.00 AC: 0 AN: 59968

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.32
BayesDel_addAF	Pathogenic	0.32	D
BayesDel_noAF	Pathogenic	0.22
CADD	Benign	23
DANN	Uncertain	0.99
DEOGEN2	Benign	0.073	T
Eigen	Uncertain	0.44
Eigen_PC	Uncertain	0.55
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Uncertain	0.95	D
M_CAP	Benign	0.045	D
MetaRNN	Uncertain	0.51	D
MetaSVM	Benign	-0.41	T
MutationAssessor	Benign	1.1	L
PhyloP100		5.8
PrimateAI	Pathogenic	0.92	D
PROVEAN	Benign	-2.1	N
REVEL	Uncertain	0.45
Sift	Benign	0.33	T
Sift4G	Benign	0.68	T
Polyphen		0.92	P
Vest4		0.67
MutPred		0.29		Loss of solvent accessibility (P = 0.0544)
MVP		0.82
MPC		1.4
ClinPred		0.84	D
GERP RS		5.9
PromoterAI		-0.00020	Neutral
Varity_R		0.17
gMVP		0.72
Mutation Taster		=29/71	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: rs368409103; hg19: chr7-28031588; COSMIC: COSV52244027;