7-127610546-AGT-A

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BA1

The NM_001366110.1(PAX4):c.*516_*517del variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0239 in 200,804 control chromosomes in the GnomAD database, including 17 homozygotes. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.0078 (15 hom., cov: 0)
  • Exomes 𝑓: 0.063 (2 hom.)
• Consequence: PAX4 NM_001366110.1 3_prime_UTR
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.286

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]

ACMG classification

Verdict is Benign. Variant got -8 ACMG points.

• BA1: GnomAdExome4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.1 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PAX4	NM_001366110.1	c.*516_*517del		3_prime_UTR_variant	12/12	ENST00000639438.3
PAX4	NM_001366111.1	c.*304_*305del		3_prime_UTR_variant	10/10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PAX4	ENST00000639438.3	c.*516_*517del		3_prime_UTR_variant	12/12	5	NM_001366110.1	A2
PAX4	ENST00000341640.6	c.*516_*517del		3_prime_UTR_variant	9/9	1

Frequencies

GnomAD3 genomes AF: 0.00776 AC: 1102 AN: 142062 Hom.: 15 Cov.: 0

Gnomad AFR AF: 0.0257

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00321

Gnomad ASJ AF: 0.000588

Gnomad EAS AF: 0.000201

Gnomad SAS AF: 0.00456

Gnomad FIN AF: 0.000614

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00125

Gnomad OTH AF: 0.00673

GnomAD4 exome AF: 0.0630 AC: 3692 AN: 58642 Hom.: 2 AF XY: 0.0632 AC XY: 1933 AN XY: 30568

Gnomad4 AFR exome AF: 0.0616

Gnomad4 AMR exome AF: 0.0520

Gnomad4 ASJ exome AF: 0.0518

Gnomad4 EAS exome AF: 0.107

Gnomad4 SAS exome AF: 0.0655

Gnomad4 FIN exome AF: 0.0651

Gnomad4 NFE exome AF: 0.0567

Gnomad4 OTH exome AF: 0.0657

GnomAD4 genome AF: 0.00780 AC: 1109 AN: 142162 Hom.: 15 Cov.: 0 AF XY: 0.00772 AC XY: 535 AN XY: 69302

Gnomad4 AFR AF: 0.0259

Gnomad4 AMR AF: 0.00320

Gnomad4 ASJ AF: 0.000588

Gnomad4 EAS AF: 0.000202

Gnomad4 SAS AF: 0.00410

Gnomad4 FIN AF: 0.000614

Gnomad4 NFE AF: 0.00125

Gnomad4 OTH AF: 0.00667

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

Maturity onset diabetes mellitus in young Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Computational scores

Source: dbNSFP v4.3

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: rs36159526; hg19: chr7-127250600;