7-127610853-T-C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The ENST00000378740.6(PAX4):c.1046A>G(p.Ter349TrpextTer2) variant causes a stop lost change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.766 in 1,536,282 control chromosomes in the GnomAD database, including 456,085 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.74 ( 42467 hom., cov: 32)

Exomes 𝑓: 0.77 ( 413618 hom. )

Consequence

PAX4
ENST00000378740.6 stop_lost

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: -0.00600

Variant links:

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]

PAX4 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_addAF=-0.851597).

BP6

Variant 7-127610853-T-C is Benign according to our data. Variant chr7-127610853-T-C is described in ClinVar as [Benign]. Clinvar id is 358791.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr7-127610853-T-C is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.777 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PAX4	NM_001366110.1 linkuse as main transcript	c.*211A>G		3_prime_UTR_variant	12/12	ENST00000639438.3
PAX4	NM_001366111.1 linkuse as main transcript	c.1046A>G	p.Ter349TrpextTer2	stop_lost	10/10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PAX4	ENST00000378740.6 linkuse as main transcript	c.1046A>G	p.Ter349TrpextTer2	stop_lost	10/10	1		P2
PAX4	ENST00000639438.3 linkuse as main transcript	c.*211A>G		3_prime_UTR_variant	12/12	5	NM_001366110.1	A2
PAX4	ENST00000341640.6 linkuse as main transcript	c.*211A>G		3_prime_UTR_variant	9/9	1			O43316-4

Frequencies

GnomAD3 genomes

AF:

0.743

AC:

112892

AN:

152022

Hom.:

42440

Cov.:

show subpopulations

Gnomad AFR

AF:

0.713

Gnomad AMI

AF:

0.797

Gnomad AMR

AF:

0.750

Gnomad ASJ

AF:

0.884

Gnomad EAS

AF:

0.368

Gnomad SAS

AF:

0.741

Gnomad FIN

AF:

0.719

Gnomad MID

AF:

0.854

Gnomad NFE

AF:

0.783

Gnomad OTH

AF:

0.744

GnomAD3 exomes

AF:

0.734

AC:

101797

AN:

138708

Hom.:

38217

AF XY:

0.736

AC XY:

55398

AN XY:

75220

show subpopulations

Gnomad AFR exome

AF:

0.709

Gnomad AMR exome

AF:

0.723

Gnomad ASJ exome

AF:

0.874

Gnomad EAS exome

AF:

0.365

Gnomad SAS exome

AF:

0.742

Gnomad FIN exome

AF:

0.732

Gnomad NFE exome

AF:

0.787

Gnomad OTH exome

AF:

0.767

GnomAD4 exome

AF:

0.769

AC:

1064249

AN:

1384142

Hom.:

413618

Cov.:

AF XY:

0.768

AC XY:

524459

AN XY:

683108

show subpopulations

Gnomad4 AFR exome

AF:

0.705

Gnomad4 AMR exome

AF:

0.732

Gnomad4 ASJ exome

AF:

0.878

Gnomad4 EAS exome

AF:

0.338

Gnomad4 SAS exome

AF:

0.743

Gnomad4 FIN exome

AF:

0.733

Gnomad4 NFE exome

AF:

0.787

Gnomad4 OTH exome

AF:

0.767

GnomAD4 genome

AF:

0.743

AC:

112969

AN:

152140

Hom.:

42467

Cov.:

AF XY:

0.736

AC XY:

54772

AN XY:

74382

show subpopulations

Gnomad4 AFR

AF:

0.713

Gnomad4 AMR

AF:

0.750

Gnomad4 ASJ

AF:

0.884

Gnomad4 EAS

AF:

0.367

Gnomad4 SAS

AF:

0.740

Gnomad4 FIN

AF:

0.719

Gnomad4 NFE

AF:

0.783

Gnomad4 OTH

AF:

0.743

Alfa

AF:

0.784

Hom.:

60163

Bravo

AF:

0.742

TwinsUK

AF:

0.773

AC:

2866

ALSPAC

AF:

0.784

AC:

3022

ExAC

AF:

0.676

AC:

14835

Asia WGS

AF:

0.582

AC:

2027

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Type 2 diabetes mellitus

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Sep 05, 2021

- -

PAX4-related disorder

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Feb 25, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Maturity onset diabetes mellitus in young

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Aug 09, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.85

BayesDel_noAF

Benign

-0.85

Cadd

Benign

Dann

Benign

0.65

Eigen

Benign

-0.65

Eigen_PC

Benign

-0.79

FATHMM_MKL

Benign

0.00026

MutationTaster

Benign

1.0

P;P;P

GERP RS

1.4

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over