7-127610546-A-AGT

Position:

• chr7-127610546-A-AGT

Variant summary

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

The NM_001366110.1(PAX4):​c.*517_*518insAC 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 0.36 (9425 hom., cov: 0)
  • Exomes 𝑓: 0.24 (298 hom.)
• Consequence: PAX4 NM_001366110.1 3_prime_UTR
• Clinical Significance: Uncertain significance criteria provided, multiple submitters, no conflicts U:2
• 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: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.428 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PAX4	NM_001366110.1	c.*517_*518insAC		3_prime_UTR_variant	12/12	ENST00000639438.3
PAX4	NM_001366111.1	c.*305_*306insAC		3_prime_UTR_variant	10/10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PAX4	ENST00000639438.3	c.*517_*518insAC		3_prime_UTR_variant	12/12	5	NM_001366110.1	A2
PAX4	ENST00000341640.6	c.*517_*518insAC		3_prime_UTR_variant	9/9	1

Frequencies

GnomAD3 genomes AF: 0.359 AC: 50966 AN: 142014 Hom.: 9417 Cov.: 0

Gnomad AFR AF: 0.218

Gnomad AMI AF: 0.441

Gnomad AMR AF: 0.428

Gnomad ASJ AF: 0.464

Gnomad EAS AF: 0.181

Gnomad SAS AF: 0.345

Gnomad FIN AF: 0.335

Gnomad MID AF: 0.474

Gnomad NFE AF: 0.432

Gnomad OTH AF: 0.379

GnomAD4 exome AF: 0.242 AC: 14753 AN: 61078 Hom.: 298 Cov.: 0 AF XY: 0.242 AC XY: 7722 AN XY: 31846

Gnomad4 AFR exome AF: 0.132

Gnomad4 AMR exome AF: 0.324

Gnomad4 ASJ exome AF: 0.291

Gnomad4 EAS exome AF: 0.0997

Gnomad4 SAS exome AF: 0.200

Gnomad4 FIN exome AF: 0.202

Gnomad4 NFE exome AF: 0.271

Gnomad4 OTH exome AF: 0.248

GnomAD4 genome AF: 0.359 AC: 50996 AN: 142114 Hom.: 9425 Cov.: 0 AF XY: 0.354 AC XY: 24504 AN XY: 69268

Gnomad4 AFR AF: 0.218

Gnomad4 AMR AF: 0.428

Gnomad4 ASJ AF: 0.464

Gnomad4 EAS AF: 0.181

Gnomad4 SAS AF: 0.346

Gnomad4 FIN AF: 0.335

Gnomad4 NFE AF: 0.432

Gnomad4 OTH AF: 0.382

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:2

Revision: criteria provided, multiple submitters, no conflicts

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

- -

not provided Uncertain:1

Uncertain significance, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

-

- -

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;