NM_175061.4:c.608G>A

Variant names:

• chr7-27832924-C-T
• rs1782734429
• NM_175061.4:c.608G>A

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2

The NM_175061.4(JAZF1):​c.608G>A​(p.Arg203His) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000411 in 1,460,560 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000041 (0 hom.)
• Consequence: JAZF1 NM_175061.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.57

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]

TAX1BP1 (HGNC:11575): (Tax1 binding protein 1) This gene encodes a HTLV-1 tax1 binding protein. The encoded protein interacts with TNFAIP3, and inhibits TNF-induced apoptosis by mediating the TNFAIP3 anti-apoptotic activity. Degradation of this protein by caspase-3-like family proteins is associated with apoptosis induced by TNF. This protein may also have a role in the inhibition of inflammatory signaling pathways. Alternatively spliced transcript variants encoding different isoforms have been found for this gene.[provided by RefSeq, May 2011]

ACMG classification

Verdict is Likely_benign. Variant got -4 ACMG points.

• BS2: High AC in GnomAdExome4 at 6 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
JAZF1	NM_175061.4	c.608G>A	p.Arg203His	missense_variant	Exon 5 of 5	ENST00000283928.10	NP_778231.2
JAZF1	XM_047420025.1	c.416G>A	p.Arg139His	missense_variant	Exon 5 of 5		XP_047275981.1
JAZF1	XM_047420026.1	c.416G>A	p.Arg139His	missense_variant	Exon 5 of 5		XP_047275982.1
JAZF1	XM_047420027.1	c.416G>A	p.Arg139His	missense_variant	Exon 6 of 6		XP_047275983.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
JAZF1	ENST00000283928.10	c.608G>A	p.Arg203His	missense_variant	Exon 5 of 5	1	NM_175061.4	ENSP00000283928.5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000411 AC: 6 AN: 1460560 Hom.: 0 Cov.: 30 AF XY: 0.00000138 AC XY: 1 AN XY: 726632

Gnomad4 AFR exome AF: 0.000120

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.0000187

Gnomad4 NFE exome AF: 9.00e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Aug 14, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.608G>A (p.R203H) alteration is located in exon 5 (coding exon 5) of the JAZF1 gene. This alteration results from a G to A substitution at nucleotide position 608, causing the arginine (R) at amino acid position 203 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	Pathogenic	0.94
BayesDel_addAF	Pathogenic	0.21	D
BayesDel_noAF	Uncertain	0.060
CADD	Pathogenic	33
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.22	T;T;T
Eigen	Uncertain	0.52
Eigen_PC	Uncertain	0.64
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.96	D;D;D
M_CAP	Benign	0.049	D
MetaRNN	Uncertain	0.54	D;D;D
MetaSVM	Benign	-0.67	T
MutationAssessor	Uncertain	2.1	M;.;.
PrimateAI	Pathogenic	0.93	D
PROVEAN	Uncertain	-3.5	D;D;N
REVEL	Uncertain	0.42
Sift	Uncertain	0.0070	D;D;D
Sift4G	Uncertain	0.0040	D;.;.
Polyphen		1.0	D;.;.
Vest4		0.74
MutPred		0.41		Loss of disorder (P = 0.132);.;.;
MVP		0.38
MPC		2.2
ClinPred		0.98	D
GERP RS		6.2
Varity_R		0.35
gMVP		0.58

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

Publications

LitVar

Other links and lift over

dbSNP: rs1782734429; hg19: chr7-27872543; COSMIC: COSV52238196; COSMIC: COSV52238196;