NM_001366110.1:c.474C>T

Variant names:

Variant summary

Our verdict is Benign. Variant got -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

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 -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 Likely_benign, oryginal submissions are: {Likely_benign=1, Benign=5, Uncertain_significance=1}.

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

GnomAD3 exomes

AF:

0.0461

AC:

11594

AN:

251452

Hom.:

386

AF XY:

0.0462

AC XY:

6273

AN XY:

135896

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 SAS exome

AF:

0.0129

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

Gnomad4 AFR exome

AF:

0.00956

Gnomad4 AMR exome

AF:

0.0251

Gnomad4 ASJ exome

AF:

0.0551

Gnomad4 EAS exome

AF:

0.000101

Gnomad4 SAS exome

AF:

0.0133

Gnomad4 FIN exome

AF:

0.0758

Gnomad4 NFE exome

AF:

0.0688

Gnomad4 OTH exome

AF:

0.0543

GnomAD4 genome

AF:

0.0455

AC:

6928

AN:

152122

Hom.:

201

Cov.:

AF XY:

0.0453

AC XY:

3366

AN XY:

74366

show subpopulations

Gnomad4 AFR

AF:

0.0117

Gnomad4 AMR

AF:

0.0298

Gnomad4 ASJ

AF:

0.0582

Gnomad4 EAS

AF:

0.000581

Gnomad4 SAS

AF:

0.0133

Gnomad4 FIN

AF:

0.0837

Gnomad4 NFE

AF:

0.0689

Gnomad4 OTH

AF:

0.0398

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

Aug 30, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

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

DANN

Benign

0.51

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

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