Genetic Variant PAX4:c.*512_*517dupACACAC (chr7-127610546-A-AGTGTGT) – ACMG Classification: Benign (-8 pts)

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BS1BS2

The NM_001366110.1(PAX4):c.*512_*517dupACACAC variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.017 ( 36 hom., cov: 0)

Exomes 𝑓: 0.0089 ( 0 hom. )

Consequence

PAX4
NM_001366110.1 3_prime_UTR

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.286

Publications

2 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

new If you want to explore the variant's impact on the transcript NM_001366110.1, check out the Mutation Effect Viewer. This is especially useful for frameshift variants or if you want to visualize the effect of exon loss / intron retention.

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -8 ACMG points.

BS1

Variant frequency is greater than expected in population sas. GnomAd4 allele frequency = 0.0174 (2482/142306) while in subpopulation SAS AF = 0.0291 (128/4392). AF 95% confidence interval is 0.025. There are 36 homozygotes in GnomAd4. There are 1167 alleles in the male GnomAd4 subpopulation. Median coverage is 0. This position passed quality control check.

BS2

High AC in GnomAd4 at 2482 AD,Unknown gene.

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.512_517dupACACAC		3_prime_UTR	Exon 12 of 12	NP_001353039.1	A0A1W2PPX4
	PAX4	NM_001366111.1		c.300_305dupACACAC		3_prime_UTR	Exon 10 of 10	NP_001353040.1	J3KPG0

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PAX4	ENST00000639438.3	TSL:5 MANE Select	c.512_517dupACACAC		3_prime_UTR	Exon 12 of 12	ENSP00000491782.1	A0A1W2PPX4
	PAX4	ENST00000341640.6	TSL:1	c.512_517dupACACAC		3_prime_UTR	Exon 9 of 9	ENSP00000339906.2	O43316-4

Frequencies

GnomAD3 genomes

AF:

0.0175

AC:

2485

AN:

142206

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0234

Gnomad AMI

AF:

0.0212

Gnomad AMR

AF:

0.00842

Gnomad ASJ

AF:

0.00764

Gnomad EAS

AF:

0.0131

Gnomad SAS

AF:

0.0296

Gnomad FIN

AF:

0.0123

Gnomad MID

AF:

0.0196

Gnomad NFE

AF:

0.0169

Gnomad OTH

AF:

0.0181

GnomAD4 exome

AF:

0.00886

AC:

551

AN:

62174

Hom.:

Cov.:

AF XY:

0.00928

AC XY:

301

AN XY:

32418

show subpopulations

African (AFR)

AF:

0.00993

AC:

AN:

2618

American (AMR)

AF:

0.00455

AC:

AN:

3294

Ashkenazi Jewish (ASJ)

AF:

0.00958

AC:

AN:

1774

East Asian (EAS)

AF:

0.00917

AC:

AN:

6110

South Asian (SAS)

AF:

0.0175

AC:

AN:

4792

European-Finnish (FIN)

AF:

0.00668

AC:

AN:

2694

Middle Eastern (MID)

AF:

0.00699

AC:

AN:

286

European-Non Finnish (NFE)

AF:

0.00818

AC:

303

AN:

37022

Other (OTH)

AF:

0.00837

AC:

AN:

3584

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.435

Heterozygous variant carriers

115

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<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:

0.0174

AC:

2482

AN:

142306

Hom.:

Cov.:

AF XY:

0.0168

AC XY:

1167

AN XY:

69390

show subpopulations

African (AFR)

AF:

0.0234

AC:

849

AN:

36358

American (AMR)

AF:

0.00841

AC:

121

AN:

14388

Ashkenazi Jewish (ASJ)

AF:

0.00764

AC:

AN:

3404

East Asian (EAS)

AF:

0.0131

AC:

AN:

4960

South Asian (SAS)

AF:

0.0291

AC:

128

AN:

4392

European-Finnish (FIN)

AF:

0.0123

AC:

121

AN:

9824

Middle Eastern (MID)

AF:

0.0177

AC:

AN:

282

European-Non Finnish (NFE)

AF:

0.0169

AC:

1113

AN:

65850

Other (OTH)

AF:

0.0179

AC:

AN:

1950

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.462

Heterozygous variant carriers

109

217

326

434

543

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

120

150

<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:

0.00915

Hom.:

301

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

0.29

Mutation Taster

=100/0

polymorphism

(source)

Splicing

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Publications

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7-127610546-AGTGTGTGT-AGTGTGTGTGTGTGT

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