rs327517

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_001366110.1(PAX4):c.543A>G(p.Gln181=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0121 in 1,613,910 control chromosomes in the GnomAD database, including 1,216 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.053 ( 624 hom., cov: 31)

Exomes 𝑓: 0.0079 ( 592 hom. )

Consequence

PAX4
NM_001366110.1 synonymous

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: 0.760

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 -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.55).

BP6

Variant 7-127613775-T-C is Benign according to our data. Variant chr7-127613775-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 129877.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.76 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.164 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.543A>G	p.Gln181=	synonymous_variant	7/12	ENST00000639438.3
PAX4	NM_001366111.1 linkuse as main transcript	c.543A>G	p.Gln181=	synonymous_variant	5/10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PAX4	ENST00000639438.3 linkuse as main transcript	c.543A>G	p.Gln181=	synonymous_variant	7/12	5	NM_001366110.1	A2

Frequencies

GnomAD3 genomes

AF:

0.0529

AC:

8041

AN:

151940

Hom.:

619

Cov.:

show subpopulations

Gnomad AFR

AF:

0.168

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0450

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.0412

Gnomad SAS

AF:

0.00560

Gnomad FIN

AF:

0.000377

Gnomad MID

AF:

0.0127

Gnomad NFE

AF:

0.00141

Gnomad OTH

AF:

0.0426

GnomAD3 exomes

AF:

0.0218

AC:

5491

AN:

251454

Hom.:

307

AF XY:

0.0167

AC XY:

2275

AN XY:

135894

show subpopulations

Gnomad AFR exome

AF:

0.173

Gnomad AMR exome

AF:

0.0464

Gnomad ASJ exome

AF:

0.0000992

Gnomad EAS exome

AF:

0.0368

Gnomad SAS exome

AF:

0.00353

Gnomad FIN exome

AF:

0.000785

Gnomad NFE exome

AF:

0.00151

Gnomad OTH exome

AF:

0.0173

GnomAD4 exome

AF:

0.00785

AC:

11478

AN:

1461852

Hom.:

592

Cov.:

AF XY:

0.00692

AC XY:

5034

AN XY:

727226

show subpopulations

Gnomad4 AFR exome

AF:

0.168

Gnomad4 AMR exome

AF:

0.0456

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0401

Gnomad4 SAS exome

AF:

0.00393

Gnomad4 FIN exome

AF:

0.000936

Gnomad4 NFE exome

AF:

0.000720

Gnomad4 OTH exome

AF:

0.0159

GnomAD4 genome

AF:

0.0530

AC:

8058

AN:

152058

Hom.:

624

Cov.:

AF XY:

0.0515

AC XY:

3830

AN XY:

74340

show subpopulations

Gnomad4 AFR

AF:

0.167

Gnomad4 AMR

AF:

0.0448

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.0411

Gnomad4 SAS

AF:

0.00561

Gnomad4 FIN

AF:

0.000377

Gnomad4 NFE

AF:

0.00141

Gnomad4 OTH

AF:

0.0422

Alfa

AF:

0.0146

Hom.:

179

Bravo

AF:

0.0624

Asia WGS

AF:

0.0310

AC:

108

AN:

3478

EpiCase

AF:

0.00131

EpiControl

AF:

0.00190

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

Likely benign, no assertion criteria provided	clinical testing	Genetic Services Laboratory, University of Chicago	-	Likely benign based on allele frequency in 1000 Genomes Project or ESP global frequency and its presence in a patient with a rare or unrelated disease phenotype. NOT Sanger confirmed. -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Sep 29, 2018	- -
Benign, criteria provided, single submitter	clinical testing	Invitae	Jan 29, 2024	- -

Maturity onset diabetes mellitus in young

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.55

Cadd

Benign

7.1

Dann

Benign

0.61

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.16

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