7-127610546-AGTGTGTGT-AGTGT

Variant names:

• chr7-127610546-AGTGT-A
• rs36159526
• NM_001366110.1:c.*514_*517delACAC

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BS1 BS2

The NM_001366110.1(PAX4):​c.*514_*517delACAC variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00894 in 204,068 control chromosomes in the GnomAD database, including 26 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.0097 (25 hom., cov: 0)
  • Exomes 𝑓: 0.0072 (1 hom.)
• Consequence: PAX4 NM_001366110.1 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.837

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]

ACMG classification

Verdict is Benign. Variant got -8 ACMG points.

• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00968 (1378/142320) while in subpopulation AFR AF= 0.0222 (809/36364). AF 95% confidence interval is 0.021. There are 25 homozygotes in gnomad4. There are 788 alleles in male gnomad4 subpopulation. Median coverage is 0. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 1378 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PAX4	NM_001366110.1	c.*514_*517delACAC		3_prime_UTR_variant	Exon 12 of 12	ENST00000639438.3	NP_001353039.1
PAX4	NM_001366111.1	c.*302_*305delACAC		3_prime_UTR_variant	Exon 10 of 10		NP_001353040.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PAX4	ENST00000639438	c.*514_*517delACAC		3_prime_UTR_variant	Exon 12 of 12	5	NM_001366110.1	ENSP00000491782.1
PAX4	ENST00000341640	c.*514_*517delACAC		3_prime_UTR_variant	Exon 9 of 9	1		ENSP00000339906.2

Frequencies

GnomAD3 genomes AF: 0.00968 AC: 1377 AN: 142220 Hom.: 25 Cov.: 0

Gnomad AFR AF: 0.0223

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00209

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000228

Gnomad FIN AF: 0.0478

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000926

Gnomad OTH AF: 0.00414

GnomAD4 exome AF: 0.00722 AC: 446 AN: 61748 Hom.: 1 AF XY: 0.00674 AC XY: 217 AN XY: 32188

Gnomad4 AFR exome AF: 0.0279

Gnomad4 AMR exome AF: 0.00307

Gnomad4 ASJ exome AF: 0.00342

Gnomad4 EAS exome AF: 0.00531

Gnomad4 SAS exome AF: 0.00273

Gnomad4 FIN exome AF: 0.0504

Gnomad4 NFE exome AF: 0.00424

Gnomad4 OTH exome AF: 0.00587

GnomAD4 genome AF: 0.00968 AC: 1378 AN: 142320 Hom.: 25 Cov.: 0 AF XY: 0.0114 AC XY: 788 AN XY: 69402

Gnomad4 AFR AF: 0.0222

Gnomad4 AMR AF: 0.00209

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000227

Gnomad4 FIN AF: 0.0478

Gnomad4 NFE AF: 0.000926

Gnomad4 OTH AF: 0.00410

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

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

Publications

LitVar

Other links and lift over

dbSNP: rs36159526; hg19: chr7-127250600;