Genetic Variant PAX4:c.*510_*517delACACACAC (chr7-127610546-AGTGTGTGT-A) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_001366110.1(PAX4):c.*510_*517delACACACAC variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000978 in 204,464 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.0000070 ( 0 hom., cov: 0)

Exomes 𝑓: 0.000016 ( 0 hom. )

Consequence

PAX4
NM_001366110.1 3_prime_UTR

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.837

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

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

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.510_517delACACACAC		3_prime_UTR	Exon 12 of 12	NP_001353039.1	A0A1W2PPX4
	PAX4	NM_001366111.1		c.298_305delACACACAC		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.510_517delACACACAC	3_prime_UTR	Exon 12 of 12	ENSP00000491782.1	A0A1W2PPX4
PAX4	ENST00000341640.6	TSL:1	c.510_517delACACACAC	3_prime_UTR	Exon 9 of 9	ENSP00000339906.2	O43316-4
PAX4	ENST00000868896.1		c.510_517delACACACAC	downstream_gene	N/A	ENSP00000538955.1

Frequencies

GnomAD3 genomes

AF:

0.00000703

AC:

AN:

142240

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000201

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:

0.0000161

AC:

AN:

62224

Hom.:

AF XY:

0.0000308

AC XY:

AN XY:

32442

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

2624

American (AMR)

AF:

0.00

AC:

AN:

3296

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

1774

East Asian (EAS)

AF:

0.00

AC:

AN:

6112

South Asian (SAS)

AF:

0.00

AC:

AN:

4796

European-Finnish (FIN)

AF:

0.000371

AC:

AN:

2694

Middle Eastern (MID)

AF:

0.00

AC:

AN:

286

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

37050

Other (OTH)

AF:

0.00

AC:

AN:

3592

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.575

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.00000703

AC:

AN:

142240

Hom.:

Cov.:

AF XY:

0.0000144

AC XY:

AN XY:

69300

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

36264

American (AMR)

AF:

0.00

AC:

AN:

14372

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3404

East Asian (EAS)

AF:

0.000201

AC:

AN:

4976

South Asian (SAS)

AF:

0.00

AC:

AN:

4390

European-Finnish (FIN)

AF:

0.00

AC:

AN:

9826

Middle Eastern (MID)

AF:

0.00

AC:

AN:

308

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

65870

Other (OTH)

AF:

0.00

AC:

AN:

1932

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.425

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.:

301

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

0.84

Splicing

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over