7-127610546-AGTGTGTGT-AGTGTGTGTGT

Variant names:

• chr7-127610546-A-AGT
• rs36159526
• NM_001366110.1:c.*516_*517dupAC

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BA1

The NM_001366110.1(PAX4):​c.*516_*517dupAC variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Uncertain significance (★★).

• Frequency:
  • Genomes: 𝑓 0.36 (9425 hom., cov: 0)
  • Exomes 𝑓: 0.24 (298 hom.)
• Consequence: PAX4 NM_001366110.1 3_prime_UTR
• Clinical Significance: Uncertain significance criteria provided, multiple submitters, no conflicts U:2
• 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.

• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.428 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.*516_*517dupAC		3_prime_UTR	Exon 12 of 12	NP_001353039.1	A0A1W2PPX4
	PAX4	NM_001366111.1		c.*304_*305dupAC		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.*516_*517dupAC		3_prime_UTR	Exon 12 of 12	ENSP00000491782.1	A0A1W2PPX4
	PAX4	ENST00000341640.6	TSL:1	c.*516_*517dupAC		3_prime_UTR	Exon 9 of 9	ENSP00000339906.2	O43316-4

Frequencies

GnomAD3 genomes AF: 0.359 AC: 50966 AN: 142014 Hom.: 9417 Cov.: 0

Gnomad AFR AF: 0.218

Gnomad AMI AF: 0.441

Gnomad AMR AF: 0.428

Gnomad ASJ AF: 0.464

Gnomad EAS AF: 0.181

Gnomad SAS AF: 0.345

Gnomad FIN AF: 0.335

Gnomad MID AF: 0.474

Gnomad NFE AF: 0.432

Gnomad OTH AF: 0.379

GnomAD4 exome AF: 0.242 AC: 14753 AN: 61078 Hom.: 298 Cov.: 0 AF XY: 0.242 AC XY: 7722 AN XY: 31846

African (AFR) AF: 0.132 AC: 342 AN: 2598

American (AMR) AF: 0.324 AC: 1049 AN: 3238

Ashkenazi Jewish (ASJ) AF: 0.291 AC: 505 AN: 1736

East Asian (EAS) AF: 0.0997 AC: 599 AN: 6006

South Asian (SAS) AF: 0.200 AC: 942 AN: 4718

European-Finnish (FIN) AF: 0.202 AC: 537 AN: 2660

Middle Eastern (MID) AF: 0.278 AC: 79 AN: 284

European-Non Finnish (NFE) AF: 0.271 AC: 9827 AN: 36316

Other (OTH) AF: 0.248 AC: 873 AN: 3522

GnomAD4 genome AF: 0.359 AC: 50996 AN: 142114 Hom.: 9425 Cov.: 0 AF XY: 0.354 AC XY: 24504 AN XY: 69268

African (AFR) AF: 0.218 AC: 7900 AN: 36308

American (AMR) AF: 0.428 AC: 6144 AN: 14362

Ashkenazi Jewish (ASJ) AF: 0.464 AC: 1579 AN: 3402

East Asian (EAS) AF: 0.181 AC: 900 AN: 4960

South Asian (SAS) AF: 0.346 AC: 1515 AN: 4382

European-Finnish (FIN) AF: 0.335 AC: 3284 AN: 9796

Middle Eastern (MID) AF: 0.468 AC: 132 AN: 282

European-Non Finnish (NFE) AF: 0.432 AC: 28404 AN: 65780

Other (OTH) AF: 0.382 AC: 742 AN: 1944

Alfa AF: 0.188 Hom.: 301

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	1	-	Maturity onset diabetes mellitus in young (1)
-	1	-	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.29
Mutation Taster		=100/0	polymorphism (auto)

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;