rs77039439

Variant names:

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_StrongBP6BP7BA1

The NM_001366110.1(PAX4):c.474C>T(p.Gly158Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0588 in 1,613,926 control chromosomes in the GnomAD database, including 3,209 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

Frequency

Genomes: 𝑓 0.046 ( 201 hom., cov: 30)

Exomes 𝑓: 0.060 ( 3008 hom. )

Consequence

PAX4
NM_001366110.1 synonymous

Scores

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1B:6

Conservation

PhyloP100: 0.211

Publications

7 publications found

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 Gene-Disease associations (from GenCC):

maturity-onset diabetes of the young
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
diabetes mellitus, noninsulin-dependent
Inheritance: Unknown Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae)
maturity-onset diabetes of the young type 9
Inheritance: Unknown Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae)
monogenic diabetes
Inheritance: AD Classification: NO_KNOWN Submitted by: ClinGen

PAX4 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.84).

BP6

Variant 7-127613844-G-A is Benign according to our data. Variant chr7-127613844-G-A is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 129876.We mark this variant Benign, oryginal submission is: [Conflicting_classifications_of_pathogenicity].

BP7

Synonymous conserved (PhyloP=0.211 with no splicing effect.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0673 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PAX4	NM_001366110.1 link	c.474C>T	p.Gly158Gly	synonymous_variant	Exon 7 of 12	ENST00000639438.3	NP_001353039.1
PAX4	NM_001366111.1 link	c.474C>T	p.Gly158Gly	synonymous_variant	Exon 5 of 10		NP_001353040.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PAX4	ENST00000639438.3 link	c.474C>T	p.Gly158Gly	synonymous_variant	Exon 7 of 12	5	NM_001366110.1	ENSP00000491782.1		A0A1W2PPX4

Frequencies

GnomAD3 genomes

AF:

0.0456

AC:

6927

AN:

152004

Hom.:

201

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0118

Gnomad AMI

AF:

0.0559

Gnomad AMR

AF:

0.0298

Gnomad ASJ

AF:

0.0582

Gnomad EAS

AF:

0.000580

Gnomad SAS

AF:

0.0131

Gnomad FIN

AF:

0.0837

Gnomad MID

AF:

0.0316

Gnomad NFE

AF:

0.0689

Gnomad OTH

AF:

0.0402

GnomAD2 exomes

AF:

0.0461

AC:

11594

AN:

251452

AF XY:

0.0462

show subpopulations

Gnomad AFR exome

AF:

0.0113

Gnomad AMR exome

AF:

0.0245

Gnomad ASJ exome

AF:

0.0574

Gnomad EAS exome

AF:

0.000163

Gnomad FIN exome

AF:

0.0790

Gnomad NFE exome

AF:

0.0668

Gnomad OTH exome

AF:

0.0458

GnomAD4 exome

AF:

0.0602

AC:

88011

AN:

1461804

Hom.:

3008

Cov.:

AF XY:

0.0589

AC XY:

42798

AN XY:

727210

show subpopulations

African (AFR)

AF:

0.00956

AC:

320

AN:

33480

American (AMR)

AF:

0.0251

AC:

1124

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.0551

AC:

1440

AN:

26136

East Asian (EAS)

AF:

0.000101

AC:

AN:

39700

South Asian (SAS)

AF:

0.0133

AC:

1146

AN:

86258

European-Finnish (FIN)

AF:

0.0758

AC:

4050

AN:

53412

Middle Eastern (MID)

AF:

0.0166

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.0688

AC:

76549

AN:

1111932

Other (OTH)

AF:

0.0543

AC:

3282

AN:

60394

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.480

Heterozygous variant carriers

4507

9013

13520

18026

22533

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0455

AC:

6928

AN:

152122

Hom.:

201

Cov.:

AF XY:

0.0453

AC XY:

3366

AN XY:

74366

show subpopulations

African (AFR)

AF:

0.0117

AC:

487

AN:

41510

American (AMR)

AF:

0.0298

AC:

455

AN:

15276

Ashkenazi Jewish (ASJ)

AF:

0.0582

AC:

202

AN:

3472

East Asian (EAS)

AF:

0.000581

AC:

AN:

5160

South Asian (SAS)

AF:

0.0133

AC:

AN:

4820

European-Finnish (FIN)

AF:

0.0837

AC:

887

AN:

10598

Middle Eastern (MID)

AF:

0.0340

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0689

AC:

4685

AN:

67968

Other (OTH)

AF:

0.0398

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.496

Heterozygous variant carriers

314

628

943

1257

1571

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.0578

Hom.:

145

Bravo

AF:

0.0410

Asia WGS

AF:

0.00577

AC:

AN:

3478

EpiCase

AF:

0.0662

EpiControl

AF:

0.0608

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:1Benign:6

Revision: criteria provided, conflicting classifications

LINK: link

Submissions by phenotype

not specified

Benign:3

Mar 27, 2013

Genetic Services Laboratory, University of Chicago

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Jul 08, 2021

Women's Health and Genetics/Laboratory Corporation of America, LabCorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Maturity onset diabetes mellitus in young

Uncertain:1Benign:1

Clinical Genomics, Uppaluri K&H Personalized Medicine Clinic

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:research

This PAX4 gene is associated with MODY, however, no association is found between this particular variant (rs77039439) of PAX4 gene and MODY yet. It needs further validation via clinical studies. -

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not provided

Benign:2

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Aug 30, 2018

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

CADD

Benign

3.4

(source)

DANN

Benign

0.51

PhyloP100

0.21

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.060

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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rs77039439

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over