7-127610546-AGTGTGTGT-AGTGTGTGTGTGTGT

Variant names:

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

Variant summary

Our verdict is Benign. Variant got -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

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 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 male gnomad4 subpopulation. Median coverage is 0. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 2482 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PAX4	NM_001366110.1	c.*512_*517dupACACAC		3_prime_UTR_variant	Exon 12 of 12	ENST00000639438.3	NP_001353039.1
PAX4	NM_001366111.1	c.*300_*305dupACACAC		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.*512_*517dupACACAC		3_prime_UTR_variant	Exon 12 of 12	5	NM_001366110.1	ENSP00000491782.1
PAX4	ENST00000341640	c.*512_*517dupACACAC		3_prime_UTR_variant	Exon 9 of 9	1		ENSP00000339906.2

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

Gnomad4 AFR exome AF: 0.00993

Gnomad4 AMR exome AF: 0.00455

Gnomad4 ASJ exome AF: 0.00958

Gnomad4 EAS exome AF: 0.00917

Gnomad4 SAS exome AF: 0.0175

Gnomad4 FIN exome AF: 0.00668

Gnomad4 NFE exome AF: 0.00818

Gnomad4 OTH exome AF: 0.00837

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

Gnomad4 AFR AF: 0.0234

Gnomad4 AMR AF: 0.00841

Gnomad4 ASJ AF: 0.00764

Gnomad4 EAS AF: 0.0131

Gnomad4 SAS AF: 0.0291

Gnomad4 FIN AF: 0.0123

Gnomad4 NFE AF: 0.0169

Gnomad4 OTH AF: 0.0179

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Splicing

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;