7-127610587-G-A

Variant names:

• chr7-127610587-G-A
• rs327520
• NM_001366110.1:c.*477C>T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001366110.1(PAX4):​c.*477C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.338 in 442,146 control chromosomes in the GnomAD database, including 29,530 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.30 (8254 hom., cov: 32)
  • Exomes 𝑓: 0.36 (21276 hom.)
• Consequence: PAX4 NM_001366110.1 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BP6: Variant 7-127610587-G-A is Benign according to our data. Variant chr7-127610587-G-A is described in ClinVar as Benign. ClinVar VariationId is 358787.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.393 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.*477C>T		3_prime_UTR	Exon 12 of 12	NP_001353039.1	A0A1W2PPX4
	PAX4	NM_001366111.1		c.*265C>T		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.*477C>T		3_prime_UTR	Exon 12 of 12	ENSP00000491782.1	A0A1W2PPX4
	PAX4	ENST00000341640.6	TSL:1	c.*477C>T		3_prime_UTR	Exon 9 of 9	ENSP00000339906.2	O43316-4
	PAX4	ENST00000378740.6	TSL:1	c.*265C>T		downstream_gene	N/A	ENSP00000368014.4	J3KPG0

Frequencies

GnomAD3 genomes AF: 0.300 AC: 45507 AN: 151752 Hom.: 8245 Cov.: 32

Gnomad AFR AF: 0.110

Gnomad AMI AF: 0.416

Gnomad AMR AF: 0.396

Gnomad ASJ AF: 0.487

Gnomad EAS AF: 0.101

Gnomad SAS AF: 0.301

Gnomad FIN AF: 0.294

Gnomad MID AF: 0.433

Gnomad NFE AF: 0.397

Gnomad OTH AF: 0.327

GnomAD4 exome AF: 0.357 AC: 103713 AN: 290276 Hom.: 21276 Cov.: 0 AF XY: 0.355 AC XY: 54434 AN XY: 153414

African (AFR) AF: 0.110 AC: 955 AN: 8698

American (AMR) AF: 0.431 AC: 5194 AN: 12056

Ashkenazi Jewish (ASJ) AF: 0.496 AC: 4311 AN: 8684

East Asian (EAS) AF: 0.109 AC: 1968 AN: 18104

South Asian (SAS) AF: 0.303 AC: 11647 AN: 38494

European-Finnish (FIN) AF: 0.297 AC: 4517 AN: 15210

Middle Eastern (MID) AF: 0.422 AC: 527 AN: 1250

European-Non Finnish (NFE) AF: 0.400 AC: 68640 AN: 171508

Other (OTH) AF: 0.366 AC: 5954 AN: 16272

GnomAD4 genome AF: 0.300 AC: 45528 AN: 151870 Hom.: 8254 Cov.: 32 AF XY: 0.296 AC XY: 21945 AN XY: 74212

African (AFR) AF: 0.110 AC: 4554 AN: 41374

American (AMR) AF: 0.396 AC: 6048 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.487 AC: 1690 AN: 3472

East Asian (EAS) AF: 0.101 AC: 519 AN: 5152

South Asian (SAS) AF: 0.302 AC: 1458 AN: 4822

European-Finnish (FIN) AF: 0.294 AC: 3093 AN: 10514

Middle Eastern (MID) AF: 0.435 AC: 127 AN: 292

European-Non Finnish (NFE) AF: 0.397 AC: 26964 AN: 67954

Other (OTH) AF: 0.331 AC: 697 AN: 2108

Alfa AF: 0.606 Hom.: 8911

Bravo AF: 0.302

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	Maturity-onset diabetes of the young (1)
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.46
DANN	Benign	0.49
PhyloP100		-0.60
Mutation Taster		=99/1	polymorphism (auto)

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: rs327520; hg19: chr7-127250641;