NM_001366110.1:c.*490_*493delGCGC

Variant names:

• chr7-127610570-TGCGC-T
• rs61297182
• NM_001366110.1:c.*490_*493delGCGC

Variant summary

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

The NM_001366110.1(PAX4):​c.*490_*493delGCGC variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000497 in 321,638 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 0.000038 (0 hom., cov: 18)
  • Exomes 𝑓: 0.000058 (0 hom.)
• Consequence: PAX4 NM_001366110.1 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.415
• Publications: 1 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: Likely_benign. The variant received -4 ACMG points.

• BS2: High AC in GnomAd4 at 5 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_*493delGCGC		3_prime_UTR	Exon 12 of 12	NP_001353039.1	A0A1W2PPX4
	PAX4	NM_001366111.1		c.*278_*281delGCGC		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.*490_*493delGCGC		3_prime_UTR	Exon 12 of 12	ENSP00000491782.1	A0A1W2PPX4
	PAX4	ENST00000341640.6	TSL:1	c.*490_*493delGCGC		3_prime_UTR	Exon 9 of 9	ENSP00000339906.2	O43316-4
	PAX4	ENST00000378740.6	TSL:1	c.*278_*281delGCGC		downstream_gene	N/A	ENSP00000368014.4	J3KPG0

Frequencies

GnomAD3 genomes AF: 0.0000380 AC: 5 AN: 131634 Hom.: 0 Cov.: 18

Gnomad AFR AF: 0.000128

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

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: 0.0000579 AC: 11 AN: 190004 Hom.: 0 AF XY: 0.0000398 AC XY: 4 AN XY: 100554

African (AFR) AF: 0.00199 AC: 11 AN: 5516

American (AMR) AF: 0.00 AC: 0 AN: 7696

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 5442

East Asian (EAS) AF: 0.00 AC: 0 AN: 12892

South Asian (SAS) AF: 0.00 AC: 0 AN: 26280

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 8970

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 752

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 112054

Other (OTH) AF: 0.00 AC: 0 AN: 10402

GnomAD4 genome AF: 0.0000380 AC: 5 AN: 131634 Hom.: 0 Cov.: 18 AF XY: 0.0000156 AC XY: 1 AN XY: 64200

African (AFR) AF: 0.000128 AC: 5 AN: 39042

American (AMR) AF: 0.00 AC: 0 AN: 12452

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2580

East Asian (EAS) AF: 0.00 AC: 0 AN: 5032

South Asian (SAS) AF: 0.00 AC: 0 AN: 4228

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 8852

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 232

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 56788

Other (OTH) AF: 0.00 AC: 0 AN: 1748

Alfa AF: 0.00 Hom.: 98

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		-0.41

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs61297182; hg19: chr7-127250624;