7-127610546-A-AGTGT

Position:

• chr7-127610546-A-AGTGT

Variant summary

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

The NM_001366110.1(PAX4):​c.*517_*518insACAC variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.0068 (3 hom., cov: 0)
  • Exomes 𝑓: 0.0056 (1 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 Likely_benign. Variant got -4 ACMG points.

• BS2: High AC in GnomAd4 at 972 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PAX4	NM_001366110.1	c.*517_*518insACAC		3_prime_UTR_variant	12/12	ENST00000639438.3	NP_001353039.1
PAX4	NM_001366111.1	c.*305_*306insACAC		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.*517_*518insACAC		3_prime_UTR_variant	12/12	5	NM_001366110.1	ENSP00000491782	A2
PAX4	ENST00000341640.6	c.*517_*518insACAC		3_prime_UTR_variant	9/9	1		ENSP00000339906

Frequencies

GnomAD3 genomes AF: 0.00679 AC: 966 AN: 142216 Hom.: 2 Cov.: 0

Gnomad AFR AF: 0.0120

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00654

Gnomad ASJ AF: 0.0259

Gnomad EAS AF: 0.00181

Gnomad SAS AF: 0.00820

Gnomad FIN AF: 0.000509

Gnomad MID AF: 0.0130

Gnomad NFE AF: 0.00427

Gnomad OTH AF: 0.00725

GnomAD4 exome AF: 0.00561 AC: 348 AN: 62014 Hom.: 1 Cov.: 0 AF XY: 0.00554 AC XY: 179 AN XY: 32330

Gnomad4 AFR exome AF: 0.00802

Gnomad4 AMR exome AF: 0.00857

Gnomad4 ASJ exome AF: 0.0243

Gnomad4 EAS exome AF: 0.000983

Gnomad4 SAS exome AF: 0.00857

Gnomad4 FIN exome AF: 0.000743

Gnomad4 NFE exome AF: 0.00501

Gnomad4 OTH exome AF: 0.00559

GnomAD4 genome AF: 0.00683 AC: 972 AN: 142316 Hom.: 3 Cov.: 0 AF XY: 0.00699 AC XY: 485 AN XY: 69400

Gnomad4 AFR AF: 0.0122

Gnomad4 AMR AF: 0.00653

Gnomad4 ASJ AF: 0.0259

Gnomad4 EAS AF: 0.00161

Gnomad4 SAS AF: 0.00819

Gnomad4 FIN AF: 0.000509

Gnomad4 NFE AF: 0.00425

Gnomad4 OTH AF: 0.00769

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

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;