chr7-127610570-T-TGTGC

Position:

• chr7-127610570-T-TGTGC

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_001366110.1(PAX4):​c.*493_*494insGCAC 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 0.020 (67 hom., cov: 18)
  • Exomes 𝑓: 0.0027 (1 hom.)
• Consequence: PAX4 NM_001366110.1 3_prime_UTR
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.415

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 -10 ACMG points.

• BP6: Variant 7-127610570-T-TGTGC is Benign according to our data. Variant chr7-127610570-T-TGTGC is described in ClinVar as [Likely_benign]. Clinvar id is 358783.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0528 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PAX4	NM_001366110.1	c.*493_*494insGCAC		3_prime_UTR_variant	12/12	ENST00000639438.3	NP_001353039.1
PAX4	NM_001366111.1	c.*281_*282insGCAC		3_prime_UTR_variant	10/10		NP_001353040.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PAX4	ENST00000639438.3	c.*493_*494insGCAC		3_prime_UTR_variant	12/12	5	NM_001366110.1	ENSP00000491782	A2
PAX4	ENST00000341640.6	c.*493_*494insGCAC		3_prime_UTR_variant	9/9	1		ENSP00000339906

Frequencies

GnomAD3 genomes AF: 0.0198 AC: 2600 AN: 131620 Hom.: 67 Cov.: 18

Gnomad AFR AF: 0.0548

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00859

Gnomad ASJ AF: 0.0132

Gnomad EAS AF: 0.0113

Gnomad SAS AF: 0.0106

Gnomad FIN AF: 0.00938

Gnomad MID AF: 0.00431

Gnomad NFE AF: 0.00188

Gnomad OTH AF: 0.0154

GnomAD4 exome AF: 0.00270 AC: 511 AN: 188962 Hom.: 1 Cov.: 0 AF XY: 0.00282 AC XY: 282 AN XY: 99978

Gnomad4 AFR exome AF: 0.0216

Gnomad4 AMR exome AF: 0.00235

Gnomad4 ASJ exome AF: 0.00517

Gnomad4 EAS exome AF: 0.00584

Gnomad4 SAS exome AF: 0.00399

Gnomad4 FIN exome AF: 0.00246

Gnomad4 NFE exome AF: 0.00102

Gnomad4 OTH exome AF: 0.00242

GnomAD4 genome AF: 0.0197 AC: 2598 AN: 131718 Hom.: 67 Cov.: 18 AF XY: 0.0196 AC XY: 1262 AN XY: 64296

Gnomad4 AFR AF: 0.0547

Gnomad4 AMR AF: 0.00858

Gnomad4 ASJ AF: 0.0132

Gnomad4 EAS AF: 0.0112

Gnomad4 SAS AF: 0.00995

Gnomad4 FIN AF: 0.00938

Gnomad4 NFE AF: 0.00188

Gnomad4 OTH AF: 0.0147

Alfa AF: 0.000930 Hom.: 0

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Maturity onset diabetes mellitus in young Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

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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: rs375106423; hg19: chr7-127250624;