PAX4 p.Arg172Arg

Variant names:

• chr7-127613801-T-T
• NM_001366110.1:c.

Your query was ambiguous. Multiple possible variants found:

• chr7-127613802--
• chr7-127613802-C-A
• chr7-127613802-C-G
• chr7-127613802-C-T
• chr7-127613804-G-T
• chr7-127613802-CCG-TCT

Variant summary

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

The NM_001366110.1(PAX4):​c. variant causes a exon region change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 30)
• Consequence: PAX4 NM_001366110.1 exon_region
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.651
• Publications: 0 publications found

Genes affected

PAX4 (HGNC:8618): (paired box 4) This gene is a member of the paired box (PAX) family of transcription factors. Members of this gene family typically contain a paired box domain, an octapeptide, and a paired-type homeodomain. These genes play critical roles during fetal development and cancer growth. The paired box 4 gene is involved in pancreatic islet development and mouse studies have demonstrated a role for this gene in differentiation of insulin-producing beta cells. [provided by RefSeq, Jul 2008]

PAX4 Gene-Disease associations (from GenCC):

• maturity-onset diabetes of the young

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• diabetes mellitus, noninsulin-dependent

  Inheritance: Unknown Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae)
• maturity-onset diabetes of the young type 9

  Inheritance: Unknown Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae)
• monogenic diabetes

  Inheritance: AD Classification: NO_KNOWN Submitted by: ClinGen

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_001366110.1. 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
	PAX4	NM_001366110.1	MANE Select	c.		exon_region	Exon 7 of 12	NP_001353039.1	A0A1W2PPX4
	PAX4	NM_001366111.1		c.		exon_region	Exon 5 of 10	NP_001353040.1	J3KPG0

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PAX4	ENST00000639438.3	TSL:5 MANE Select	c.		exon_region	Exon 7 of 12	ENSP00000491782.1	A0A1W2PPX4
	PAX4	ENST00000378740.6	TSL:1	c.		exon_region	Exon 5 of 10	ENSP00000368014.4	J3KPG0
	PAX4	ENST00000341640.6	TSL:1	c.		exon_region	Exon 4 of 9	ENSP00000339906.2	O43316-4

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 30

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.65

Splicing

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr7-127253855;