ENST00000378740.6:c.1025C>T

Variant names:

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The ENST00000378740.6(PAX4):c.1025C>T(p.Thr342Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000723 in 1,539,682 control chromosomes in the GnomAD database, including 11 homozygotes. In-silico tool predicts a benign outcome for this variant. 11/12 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0039 ( 4 hom., cov: 33)

Exomes 𝑓: 0.00037 ( 7 hom. )

Consequence

PAX4
ENST00000378740.6 missense

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 0.0100

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 -16 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0049016774).

BP6

Variant 7-127610874-G-A is Benign according to our data. Variant chr7-127610874-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 358792.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High AC in GnomAd4 at 599 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PAX4	NM_001366110.1 link	c.*190C>T		3_prime_UTR_variant	Exon 12 of 12	ENST00000639438.3	NP_001353039.1
PAX4	NM_001366111.1 link	c.1025C>T	p.Thr342Ile	missense_variant	Exon 10 of 10		NP_001353040.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PAX4	ENST00000639438 link	c.*190C>T		3_prime_UTR_variant	Exon 12 of 12	5	NM_001366110.1	ENSP00000491782.1		A0A1W2PPX4

Frequencies

GnomAD3 genomes

AF:

0.00394

AC:

599

AN:

152216

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0139

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00124

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00191

GnomAD3 exomes

AF:

0.00100

AC:

141

AN:

140410

Hom.:

AF XY:

0.000697

AC XY:

AN XY:

76038

show subpopulations

Gnomad AFR exome

AF:

0.0185

Gnomad AMR exome

AF:

0.000611

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000444

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000179

Gnomad OTH exome

AF:

0.000238

GnomAD4 exome

AF:

0.000370

AC:

514

AN:

1387348

Hom.:

Cov.:

AF XY:

0.000307

AC XY:

210

AN XY:

684600

show subpopulations

Gnomad4 AFR exome

AF:

0.0138

Gnomad4 AMR exome

AF:

0.000672

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000252

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000834

Gnomad4 OTH exome

AF:

0.000656

GnomAD4 genome

AF:

0.00393

AC:

599

AN:

152334

Hom.:

Cov.:

AF XY:

0.00375

AC XY:

279

AN XY:

74494

show subpopulations

Gnomad4 AFR

AF:

0.0138

Gnomad4 AMR

AF:

0.00124

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00189

Alfa

AF:

0.00198

Hom.:

Bravo

AF:

0.00472

ExAC

AF:

0.000592

AC:

Asia WGS

AF:

0.000577

AC:

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Aug 31, 2022

Genetic Services Laboratory, University of Chicago

Significance: Likely benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

PAX4-related disorder

Benign:1

Jun 26, 2019

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

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

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not provided

Benign:1

Dec 12, 2018

GeneDx

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.61

BayesDel_noAF

Benign

-0.63

CADD

Benign

2.6

DANN

Benign

0.27

Eigen

Benign

-0.88

Eigen_PC

Benign

-0.96

FATHMM_MKL

Benign

0.0093

LIST_S2

Benign

0.36

T;T

MetaRNN

Benign

0.0049

T;T

MetaSVM

Benign

-0.99

PROVEAN

Benign

-0.44

N;.

REVEL

Benign

0.096

Sift

Benign

0.092

T;.

Sift4G

Benign

0.48

.;T

Vest4

0.13

MVP

0.19

ClinPred

0.00049

GERP RS

-0.095

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