Genetic Variant PAX4:c.*490_*493dupGCGC (chr7-127610570-T-TGCGC) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BS2

The NM_001366110.1(PAX4):c.*490_*493dupGCGC 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 0.000030 ( 0 hom., cov: 18)

Exomes 𝑓: 0.00014 ( 0 hom. )

Consequence

PAX4
NM_001366110.1 3_prime_UTR

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.415

Publications

1 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: Likely_benign. The variant received -4 ACMG points.

BS2

High AC in GnomAdExome4 at 27 Unknown,AD 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.490_493dupGCGC		3_prime_UTR	Exon 12 of 12	NP_001353039.1	A0A1W2PPX4
	PAX4	NM_001366111.1		c.278_281dupGCGC		3_prime_UTR	Exon 10 of 10	NP_001353040.1	J3KPG0

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
PAX4	ENST00000639438.3	TSL:5 MANE Select	c.490_493dupGCGC	3_prime_UTR	Exon 12 of 12	ENSP00000491782.1	A0A1W2PPX4
PAX4	ENST00000341640.6	TSL:1	c.490_493dupGCGC	3_prime_UTR	Exon 9 of 9	ENSP00000339906.2	O43316-4
PAX4	ENST00000378740.6	TSL:1	c.278_281dupGCGC	downstream_gene	N/A	ENSP00000368014.4	J3KPG0

Frequencies

GnomAD3 genomes

AF:

0.0000304

AC:

AN:

131634

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000768

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000803

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.000142

AC:

AN:

190004

Hom.:

Cov.:

AF XY:

0.000149

AC XY:

AN XY:

100548

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

5526

American (AMR)

AF:

0.00

AC:

AN:

7696

Ashkenazi Jewish (ASJ)

AF:

0.000184

AC:

AN:

5442

East Asian (EAS)

AF:

0.00

AC:

AN:

12892

South Asian (SAS)

AF:

0.000419

AC:

AN:

26276

European-Finnish (FIN)

AF:

0.000223

AC:

AN:

8970

Middle Eastern (MID)

AF:

0.00

AC:

AN:

752

European-Non Finnish (NFE)

AF:

0.000107

AC:

AN:

112048

Other (OTH)

AF:

0.0000961

AC:

AN:

10402

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.488

Heterozygous variant carriers

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:

0.0000304

AC:

AN:

131732

Hom.:

Cov.:

AF XY:

0.0000467

AC XY:

AN XY:

64298

show subpopulations

African (AFR)

AF:

0.0000766

AC:

AN:

39150

American (AMR)

AF:

0.0000802

AC:

AN:

12468

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2580

East Asian (EAS)

AF:

0.00

AC:

AN:

5018

South Asian (SAS)

AF:

0.00

AC:

AN:

4220

European-Finnish (FIN)

AF:

0.00

AC:

AN:

8852

Middle Eastern (MID)

AF:

0.00

AC:

AN:

216

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

56782

Other (OTH)

AF:

0.00

AC:

AN:

1766

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.550

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome 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

Alfa

AF:

0.00

Hom.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

-0.41

Splicing

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

Publications

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7-127610570-TGCGC-TGCGCGCGC

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