7-127610572-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_001366110.1(PAX4):c.*492G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0164 in 275,170 control chromosomes in the GnomAD database, including 46 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.033 (29 hom., cov: 31)
  • Exomes 𝑓: 0.010 (17 hom.)
• Consequence: PAX4 NM_001366110.1 3_prime_UTR
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.29

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BP6: Variant 7-127610572-C-T is Benign according to our data. Variant chr7-127610572-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 358784.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.0328 (2493/76080) while in subpopulation SAS AF= 0.0527 (127/2410). AF 95% confidence interval is 0.0479. There are 29 homozygotes in gnomad4. There are 1172 alleles in male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck.
• BS2: High AC in GnomAd at 2487 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PAX4	NM_001366110.1	c.*492G>A		3_prime_UTR_variant	12/12	ENST00000639438.3
PAX4	NM_001366111.1	c.*280G>A		3_prime_UTR_variant	10/10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PAX4	ENST00000639438.3	c.*492G>A		3_prime_UTR_variant	12/12	5	NM_001366110.1	A2
PAX4	ENST00000341640.6	c.*492G>A		3_prime_UTR_variant	9/9	1

Frequencies

GnomAD3 genomes AF: 0.0327 AC: 2487 AN: 76024 Hom.: 29 Cov.: 31

Gnomad AFR AF: 0.0505

Gnomad AMI AF: 0.0864

Gnomad AMR AF: 0.0204

Gnomad ASJ AF: 0.0169

Gnomad EAS AF: 0.00520

Gnomad SAS AF: 0.0532

Gnomad FIN AF: 0.0221

Gnomad MID AF: 0.0462

Gnomad NFE AF: 0.0304

Gnomad OTH AF: 0.0288

GnomAD4 exome AF: 0.0101 AC: 2012 AN: 199090 Hom.: 17 Cov.: 0 AF XY: 0.0106 AC XY: 1123 AN XY: 105922

Gnomad4 AFR exome AF: 0.0172

Gnomad4 AMR exome AF: 0.00482

Gnomad4 ASJ exome AF: 0.00682

Gnomad4 EAS exome AF: 0.00214

Gnomad4 SAS exome AF: 0.0164

Gnomad4 FIN exome AF: 0.00795

Gnomad4 NFE exome AF: 0.00990

Gnomad4 OTH exome AF: 0.00917

GnomAD4 genome AF: 0.0328 AC: 2493 AN: 76080 Hom.: 29 Cov.: 31 AF XY: 0.0316 AC XY: 1172 AN XY: 37136

Gnomad4 AFR AF: 0.0507

Gnomad4 AMR AF: 0.0204

Gnomad4 ASJ AF: 0.0169

Gnomad4 EAS AF: 0.00521

Gnomad4 SAS AF: 0.0527

Gnomad4 FIN AF: 0.0221

Gnomad4 NFE AF: 0.0304

Gnomad4 OTH AF: 0.0303

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

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
Cadd	Benign	0.39
Dann	Benign	0.47

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: rs405576; hg19: chr7-127250626; COSMIC: COSV58389037; COSMIC: COSV58389037;