rs644242

Variant names:

• chr11-31791253-C-A
• rs644242
• NM_001368894.2:c.1075-393G>T

Your query was ambiguous. Multiple possible variants found:

• chr11-31791253-C-A
• chr11-31791253-C-G
• chr11-31791253-C-T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001368894.2(PAX6):​c.1075-393G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0655 in 355,048 control chromosomes in the GnomAD database, including 1,073 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.061 (397 hom., cov: 32)
  • Exomes 𝑓: 0.069 (676 hom.)
• Consequence: PAX6 NM_001368894.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0730
• Publications: 16 publications found

Genes affected

PAX6 (HGNC:8620): (paired box 6) This gene encodes paired box protein Pax-6, one of many human homologs of the Drosophila melanogaster gene prd. In addition to a conserved paired box domain, a hallmark feature of this gene family, the encoded protein also contains a homeobox domain. Both domains are known to bind DNA and function as regulators of gene transcription. Activity of this protein is key in the development of neural tissues, particularly the eye. This gene is regulated by multiple enhancers located up to hundreds of kilobases distant from this locus. Mutations in this gene or in the enhancer regions can cause ocular disorders such as aniridia and Peter's anomaly. Use of alternate promoters and alternative splicing results in multiple transcript variants encoding different isoforms. Interestingly, inclusion of a particular alternate coding exon has been shown to increase the length of the paired box domain and alter its DNA binding specificity. Consequently, isoforms that carry the shorter paired box domain regulate a different set of genes compared to the isoforms carrying the longer paired box domain. [provided by RefSeq, Mar 2019]

PAX6 Gene-Disease associations (from GenCC):

• aniridia 1

  Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: Genomics England PanelApp, G2P, Labcorp Genetics (formerly Invitae)
• PAX6-related ocular dysgenesis

  Inheritance: AD Classification: DEFINITIVE Submitted by: ClinGen
• Peters anomaly

  Inheritance: AD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: PanelApp Australia, G2P, Orphanet, Labcorp Genetics (formerly Invitae)
• coloboma, ocular, autosomal dominant

  Inheritance: AD Classification: STRONG Submitted by: PanelApp Australia
• diabetes mellitus

  Inheritance: AD Classification: STRONG Submitted by: Genomics England PanelApp
• aniridia-cerebellar ataxia-intellectual disability syndrome

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• foveal hypoplasia-presenile cataract syndrome

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• isolated aniridia

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• isolated optic nerve hypoplasia

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• autosomal dominant keratitis

  Inheritance: Unknown, AD Classification: SUPPORTIVE, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Orphanet

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.61).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.182 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PAX6	NM_001368894.2	c.1075-393G>T		intron_variant	Intron 12 of 13	ENST00000640368.2	NP_001355823.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PAX6	ENST00000640368.2	c.1075-393G>T		intron_variant	Intron 12 of 13	5	NM_001368894.2	ENSP00000492024.1

Frequencies

GnomAD3 genomes AF: 0.0613 AC: 9324 AN: 152074 Hom.: 397 Cov.: 32

Gnomad AFR AF: 0.0405

Gnomad AMI AF: 0.00548

Gnomad AMR AF: 0.130

Gnomad ASJ AF: 0.0717

Gnomad EAS AF: 0.191

Gnomad SAS AF: 0.0690

Gnomad FIN AF: 0.0498

Gnomad MID AF: 0.146

Gnomad NFE AF: 0.0493

Gnomad OTH AF: 0.0727

GnomAD4 exome AF: 0.0686 AC: 13923 AN: 202856 Hom.: 676 Cov.: 0 AF XY: 0.0681 AC XY: 7456 AN XY: 109432

African (AFR) AF: 0.0417 AC: 241 AN: 5778

American (AMR) AF: 0.170 AC: 1869 AN: 10996

Ashkenazi Jewish (ASJ) AF: 0.0781 AC: 386 AN: 4942

East Asian (EAS) AF: 0.184 AC: 1733 AN: 9444

South Asian (SAS) AF: 0.0726 AC: 2628 AN: 36208

European-Finnish (FIN) AF: 0.0528 AC: 497 AN: 9412

Middle Eastern (MID) AF: 0.112 AC: 83 AN: 744

European-Non Finnish (NFE) AF: 0.0497 AC: 5724 AN: 115072

Other (OTH) AF: 0.0743 AC: 762 AN: 10260

GnomAD4 genome AF: 0.0612 AC: 9319 AN: 152192 Hom.: 397 Cov.: 32 AF XY: 0.0636 AC XY: 4730 AN XY: 74398

African (AFR) AF: 0.0405 AC: 1682 AN: 41536

American (AMR) AF: 0.130 AC: 1990 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.0717 AC: 249 AN: 3472

East Asian (EAS) AF: 0.192 AC: 986 AN: 5148

South Asian (SAS) AF: 0.0682 AC: 329 AN: 4822

European-Finnish (FIN) AF: 0.0498 AC: 528 AN: 10592

Middle Eastern (MID) AF: 0.150 AC: 44 AN: 294

European-Non Finnish (NFE) AF: 0.0493 AC: 3354 AN: 68018

Other (OTH) AF: 0.0719 AC: 152 AN: 2114

Alfa AF: 0.0444 Hom.: 123

Bravo AF: 0.0701

Asia WGS AF: 0.139 AC: 481 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.61
CADD	Benign	4.6
DANN	Benign	0.78
PhyloP100		-0.073
Mutation Taster		=100/0	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: rs644242; hg19: chr11-31812801;