7-127610570-TGCGC-TGCGCGC

Variant names:

• chr7-127610570-T-TGC
• rs61297182
• NM_001366110.1:c.*492_*493dupGC

Variant summary

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

The NM_001366110.1(PAX4):​c.*492_*493dupGC variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.23 (3019 hom., cov: 18)
  • Exomes 𝑓: 0.14 (2427 hom.)
• Consequence: PAX4 NM_001366110.1 3_prime_UTR
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• 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: Benign. The variant received -10 ACMG points.

• BP6: Variant 7-127610570-T-TGC is Benign according to our data. Variant chr7-127610570-T-TGC is described in ClinVar as Likely_benign. ClinVar VariationId is 358782.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.31 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.*492_*493dupGC		3_prime_UTR	Exon 12 of 12	NP_001353039.1	A0A1W2PPX4
	PAX4	NM_001366111.1		c.*280_*281dupGC		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.*492_*493dupGC		3_prime_UTR	Exon 12 of 12	ENSP00000491782.1	A0A1W2PPX4
	PAX4	ENST00000341640.6	TSL:1	c.*492_*493dupGC		3_prime_UTR	Exon 9 of 9	ENSP00000339906.2	O43316-4
	PAX4	ENST00000378740.6	TSL:1	c.*280_*281dupGC		downstream_gene	N/A	ENSP00000368014.4	J3KPG0

Frequencies

GnomAD3 genomes AF: 0.229 AC: 30112 AN: 131484 Hom.: 3017 Cov.: 18

Gnomad AFR AF: 0.209

Gnomad AMI AF: 0.158

Gnomad AMR AF: 0.217

Gnomad ASJ AF: 0.216

Gnomad EAS AF: 0.137

Gnomad SAS AF: 0.326

Gnomad FIN AF: 0.208

Gnomad MID AF: 0.172

Gnomad NFE AF: 0.251

Gnomad OTH AF: 0.228

GnomAD4 exome AF: 0.145 AC: 26332 AN: 181612 Hom.: 2427 Cov.: 0 AF XY: 0.149 AC XY: 14324 AN XY: 96050

African (AFR) AF: 0.163 AC: 863 AN: 5308

American (AMR) AF: 0.103 AC: 760 AN: 7352

Ashkenazi Jewish (ASJ) AF: 0.106 AC: 552 AN: 5228

East Asian (EAS) AF: 0.0759 AC: 963 AN: 12680

South Asian (SAS) AF: 0.204 AC: 5090 AN: 24910

European-Finnish (FIN) AF: 0.130 AC: 1131 AN: 8698

Middle Eastern (MID) AF: 0.125 AC: 90 AN: 720

European-Non Finnish (NFE) AF: 0.146 AC: 15537 AN: 106748

Other (OTH) AF: 0.135 AC: 1346 AN: 9968

GnomAD4 genome AF: 0.229 AC: 30127 AN: 131580 Hom.: 3019 Cov.: 18 AF XY: 0.228 AC XY: 14653 AN XY: 64218

African (AFR) AF: 0.209 AC: 8166 AN: 39110

American (AMR) AF: 0.217 AC: 2706 AN: 12452

Ashkenazi Jewish (ASJ) AF: 0.216 AC: 558 AN: 2580

East Asian (EAS) AF: 0.136 AC: 683 AN: 5014

South Asian (SAS) AF: 0.325 AC: 1369 AN: 4216

European-Finnish (FIN) AF: 0.208 AC: 1838 AN: 8824

Middle Eastern (MID) AF: 0.190 AC: 41 AN: 216

European-Non Finnish (NFE) AF: 0.251 AC: 14259 AN: 56726

Other (OTH) AF: 0.227 AC: 400 AN: 1764

Alfa AF: 0.0829 Hom.: 98

ClinVar

ClinVar submissions as Germline

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	Maturity onset diabetes mellitus in young (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		-0.41
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: rs61297182; hg19: chr7-127250624;