7-127610586-C-CACAT

Variant names:

• chr7-127610586-C-CACAT
• rs200757052
• NM_001366110.1:c.*477_*478insATGT

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_001366110.1(PAX4):​c.*477_*478insATGT variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.364 in 401,558 control chromosomes in the GnomAD database, including 28,303 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.40 (8243 hom., cov: 32)
  • Exomes 𝑓: 0.35 (20060 hom.)
• Consequence: PAX4 NM_001366110.1 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.601
• 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 -10 ACMG points.

• BP6: Variant 7-127610586-C-CACAT is Benign according to our data. Variant chr7-127610586-C-CACAT is described in ClinVar as Benign. ClinVar VariationId is 358785.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.474 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.*477_*478insATGT		3_prime_UTR	Exon 12 of 12	NP_001353039.1	A0A1W2PPX4
	PAX4	NM_001366111.1		c.*265_*266insATGT		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.*477_*478insATGT		3_prime_UTR	Exon 12 of 12	ENSP00000491782.1	A0A1W2PPX4
	PAX4	ENST00000341640.6	TSL:1	c.*477_*478insATGT		3_prime_UTR	Exon 9 of 9	ENSP00000339906.2	O43316-4
	PAX4	ENST00000378740.6	TSL:1	c.*265_*266insATGT		downstream_gene	N/A	ENSP00000368014.4	J3KPG0

Frequencies

GnomAD3 genomes AF: 0.396 AC: 45478 AN: 114758 Hom.: 8234 Cov.: 32

Gnomad AFR AF: 0.191

Gnomad AMI AF: 0.496

Gnomad AMR AF: 0.472

Gnomad ASJ AF: 0.582

Gnomad EAS AF: 0.115

Gnomad SAS AF: 0.396

Gnomad FIN AF: 0.381

Gnomad MID AF: 0.562

Gnomad NFE AF: 0.478

Gnomad OTH AF: 0.420

GnomAD4 exome AF: 0.351 AC: 100666 AN: 286736 Hom.: 20060 Cov.: 0 AF XY: 0.348 AC XY: 52775 AN XY: 151438

African (AFR) AF: 0.109 AC: 941 AN: 8604

American (AMR) AF: 0.425 AC: 4961 AN: 11686

Ashkenazi Jewish (ASJ) AF: 0.496 AC: 4227 AN: 8518

East Asian (EAS) AF: 0.0985 AC: 1921 AN: 19510

South Asian (SAS) AF: 0.301 AC: 11325 AN: 37634

European-Finnish (FIN) AF: 0.287 AC: 4315 AN: 15024

Middle Eastern (MID) AF: 0.425 AC: 522 AN: 1228

European-Non Finnish (NFE) AF: 0.396 AC: 66632 AN: 168472

Other (OTH) AF: 0.363 AC: 5822 AN: 16060

GnomAD4 genome AF: 0.396 AC: 45499 AN: 114822 Hom.: 8243 Cov.: 32 AF XY: 0.390 AC XY: 21927 AN XY: 56162

African (AFR) AF: 0.190 AC: 4555 AN: 23924

American (AMR) AF: 0.472 AC: 6040 AN: 12786

Ashkenazi Jewish (ASJ) AF: 0.582 AC: 1688 AN: 2898

East Asian (EAS) AF: 0.115 AC: 514 AN: 4470

South Asian (SAS) AF: 0.397 AC: 1457 AN: 3674

European-Finnish (FIN) AF: 0.381 AC: 3092 AN: 8108

Middle Eastern (MID) AF: 0.557 AC: 127 AN: 228

European-Non Finnish (NFE) AF: 0.478 AC: 26951 AN: 56326

Other (OTH) AF: 0.423 AC: 697 AN: 1646

Alfa AF: 0.0834 Hom.: 213

Asia WGS AF: 0.221 AC: 762 AN: 3460

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	Maturity-onset diabetes of the young (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		-0.60
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: rs200757052; hg19: chr7-127250640;