7-127610393-CAT-C

Position:

• chr7-127610393-CAT-C

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_001366110.1(PAX4):​c.*669_*670del variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0548 in 158,650 control chromosomes in the GnomAD database, including 704 homozygotes. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.057 (701 hom., cov: 32)
  • Exomes 𝑓: 0.010 (3 hom.)
• Consequence: PAX4 NM_001366110.1 3_prime_UTR
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.0850

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 -10 ACMG points.

• BP6: Variant 7-127610393-CAT-C is Benign according to our data. Variant chr7-127610393-CAT-C is described in ClinVar as [Likely_benign]. Clinvar id is 358774.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.176 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PAX4	NM_001366110.1	c.*669_*670del		3_prime_UTR_variant	12/12	ENST00000639438.3	NP_001353039.1
PAX4	NM_001366111.1	c.*457_*458del		3_prime_UTR_variant	10/10		NP_001353040.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PAX4	ENST00000639438.3	c.*669_*670del		3_prime_UTR_variant	12/12	5	NM_001366110.1	ENSP00000491782	A2
PAX4	ENST00000341640.6	c.*669_*670del		3_prime_UTR_variant	9/9	1		ENSP00000339906

Frequencies

GnomAD3 genomes AF: 0.0567 AC: 8610 AN: 151912 Hom.: 696 Cov.: 32

Gnomad AFR AF: 0.179

Gnomad AMI AF: 0.0252

Gnomad AMR AF: 0.0467

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.0415

Gnomad SAS AF: 0.00539

Gnomad FIN AF: 0.000378

Gnomad MID AF: 0.0159

Gnomad NFE AF: 0.00152

Gnomad OTH AF: 0.0480

GnomAD4 exome AF: 0.0103 AC: 68 AN: 6622 Hom.: 3 AF XY: 0.0111 AC XY: 38 AN XY: 3432

Gnomad4 AFR exome AF: 0.196

Gnomad4 AMR exome AF: 0.0252

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0455

Gnomad4 SAS exome AF: 0.00485

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00102

Gnomad4 OTH exome AF: 0.00481

GnomAD4 genome AF: 0.0568 AC: 8632 AN: 152028 Hom.: 701 Cov.: 32 AF XY: 0.0554 AC XY: 4120 AN XY: 74342

Gnomad4 AFR AF: 0.179

Gnomad4 AMR AF: 0.0466

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.0414

Gnomad4 SAS AF: 0.00540

Gnomad4 FIN AF: 0.000378

Gnomad4 NFE AF: 0.00152

Gnomad4 OTH AF: 0.0475

Alfa AF: 0.0326 Hom.: 54

Bravo AF: 0.0669

Asia WGS AF: 0.0320 AC: 111 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Maturity onset diabetes mellitus in young Benign:1

Likely benign, 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: rs59241875; hg19: chr7-127250447;