dbSNP rs77039439: PAX4:p.Gly158Gly (chr7-127613844-G-A) – ACMG Classification: Benign (-14 pts)

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 VariationId is 129876.

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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001366110.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PAX4	NM_001366110.1	MANE Select	c.474C>T	p.Gly158Gly	synonymous	Exon 7 of 12	NP_001353039.1	A0A1W2PPX4
	PAX4	NM_001366111.1		c.474C>T	p.Gly158Gly	synonymous	Exon 5 of 10	NP_001353040.1	J3KPG0

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
PAX4	ENST00000639438.3	TSL:5 MANE Select	c.474C>T	p.Gly158Gly	synonymous	Exon 7 of 12	ENSP00000491782.1	A0A1W2PPX4
PAX4	ENST00000378740.6	TSL:1	c.474C>T	p.Gly158Gly	synonymous	Exon 5 of 10	ENSP00000368014.4	J3KPG0
PAX4	ENST00000341640.6	TSL:1	c.450C>T	p.Gly150Gly	synonymous	Exon 4 of 9	ENSP00000339906.2	O43316-4

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

Age Distribution

Exome Het

Exome Hom

Variant carriers

2732

5464

8196

10928

13660

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

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

Age Distribution

Genome Het

Genome Hom

Variant carriers

160

240

320

400

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

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

ClinVar submissions

Significance:Conflicting classifications of pathogenicity

Revision:criteria provided, conflicting classifications

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (3)

Maturity-onset diabetes of the young (2)

not provided (2)

Computational scores

Source: dbNSFP v4.9

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over