7-127610662-A-G

Position:

• chr7-127610662-A-G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001366110.1(PAX4):​c.*402T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0286 in 596,872 control chromosomes in the GnomAD database, including 1,570 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.072 (1172 hom., cov: 34)
  • Exomes 𝑓: 0.014 (398 hom.)
• Consequence: PAX4 NM_001366110.1 3_prime_UTR
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 1.25

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BP6: Variant 7-127610662-A-G is Benign according to our data. Variant chr7-127610662-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 358789.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.228 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PAX4	NM_001366110.1	c.*402T>C		3_prime_UTR_variant	12/12	ENST00000639438.3	NP_001353039.1
PAX4	NM_001366111.1	c.*190T>C		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.*402T>C		3_prime_UTR_variant	12/12	5	NM_001366110.1	ENSP00000491782	A2
PAX4	ENST00000341640.6	c.*402T>C		3_prime_UTR_variant	9/9	1		ENSP00000339906

Frequencies

GnomAD3 genomes AF: 0.0717 AC: 10913 AN: 152198 Hom.: 1164 Cov.: 34

Gnomad AFR AF: 0.232

Gnomad AMI AF: 0.0252

Gnomad AMR AF: 0.0534

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.0413

Gnomad SAS AF: 0.00538

Gnomad FIN AF: 0.000376

Gnomad MID AF: 0.0158

Gnomad NFE AF: 0.00160

Gnomad OTH AF: 0.0554

GnomAD4 exome AF: 0.0137 AC: 6101 AN: 444556 Hom.: 398 Cov.: 3 AF XY: 0.0119 AC XY: 2783 AN XY: 233994

Gnomad4 AFR exome AF: 0.226

Gnomad4 AMR exome AF: 0.0459

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0399

Gnomad4 SAS exome AF: 0.00386

Gnomad4 FIN exome AF: 0.00111

Gnomad4 NFE exome AF: 0.00132

Gnomad4 OTH exome AF: 0.0246

GnomAD4 genome AF: 0.0718 AC: 10942 AN: 152316 Hom.: 1172 Cov.: 34 AF XY: 0.0693 AC XY: 5162 AN XY: 74510

Gnomad4 AFR AF: 0.232

Gnomad4 AMR AF: 0.0532

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.0412

Gnomad4 SAS AF: 0.00538

Gnomad4 FIN AF: 0.000376

Gnomad4 NFE AF: 0.00160

Gnomad4 OTH AF: 0.0549

Alfa AF: 0.0427 Hom.: 138

Bravo AF: 0.0837

Asia WGS AF: 0.0330 AC: 116 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

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

- -

not provided Benign:1

Likely benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

-

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	7.8
DANN	Benign	0.46

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: rs327519; hg19: chr7-127250716;