7-127610546-AGTGTGTGT-AGTGTGTGTGTGTGT

Variant names:

• chr7-127610546-A-AGTGTGT
• rs36159526
• NM_001366110.1:c.*512_*517dupACACAC

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BS1 BS2

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.286
• Publications: 2 publications found

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

ACMG classification

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 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.*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.: 36 Cov.: 0

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.: 0 Cov.: 0 AF XY: 0.00928 AC XY: 301 AN XY: 32418

African (AFR) AF: 0.00993 AC: 26 AN: 2618

American (AMR) AF: 0.00455 AC: 15 AN: 3294

Ashkenazi Jewish (ASJ) AF: 0.00958 AC: 17 AN: 1774

East Asian (EAS) AF: 0.00917 AC: 56 AN: 6110

South Asian (SAS) AF: 0.0175 AC: 84 AN: 4792

European-Finnish (FIN) AF: 0.00668 AC: 18 AN: 2694

Middle Eastern (MID) AF: 0.00699 AC: 2 AN: 286

European-Non Finnish (NFE) AF: 0.00818 AC: 303 AN: 37022

Other (OTH) AF: 0.00837 AC: 30 AN: 3584

GnomAD4 genome AF: 0.0174 AC: 2482 AN: 142306 Hom.: 36 Cov.: 0 AF XY: 0.0168 AC XY: 1167 AN XY: 69390

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: 26 AN: 3404

East Asian (EAS) AF: 0.0131 AC: 65 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: 5 AN: 282

European-Non Finnish (NFE) AF: 0.0169 AC: 1113 AN: 65850

Other (OTH) AF: 0.0179 AC: 35 AN: 1950

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

Splicing

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

Other links and lift over

dbSNP: rs36159526; hg19: chr7-127250600;