chr9-4483189-T-C

Variant names:

• chr9-4483189-T-C
• rs10491733
• ENST00000818379.1:n.696+6439A>G

Variant summary

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

The ENST00000818379.1(ENSG00000306426):​n.696+6439A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.524 in 151,160 control chromosomes in the GnomAD database, including 20,973 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 0.52 (20973 hom., cov: 31)
• Consequence: ENSG00000306426 ENST00000818379.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.160
• Publications: 7 publications found

Genes affected

ENSG00000306426 (HGNC:):

GLIS3 (HGNC:28510): (GLIS family zinc finger 3) This gene is a member of the GLI-similar zinc finger protein family and encodes a nuclear protein with five C2H2-type zinc finger domains. This protein functions as both a repressor and activator of transcription and is specifically involved in the development of pancreatic beta cells, the thyroid, eye, liver and kidney. Mutations in this gene have been associated with neonatal diabetes and congenital hypothyroidism (NDH). Alternatively spliced variants that encode different protein isoforms have been described but the full-length nature of only two have been determined. [provided by RefSeq, Jul 2008]

GLIS3 Gene-Disease associations (from GenCC):

• neonatal diabetes mellitus with congenital hypothyroidism

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Orphanet, G2P, Ambry Genetics, Labcorp Genetics (formerly Invitae), Genomics England PanelApp
• Tourette syndrome

  Inheritance: Unknown Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae)

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.727 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GLIS3	XM_047422890.1	c.-152+6439A>G		intron_variant	Intron 1 of 11		XP_047278846.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ENSG00000306426	ENST00000818379.1	n.696+6439A>G		intron_variant	Intron 1 of 1
ENSG00000306426	ENST00000818380.1	n.377+6677A>G		intron_variant	Intron 1 of 1
ENSG00000306426	ENST00000818381.1	n.231+6677A>G		intron_variant	Intron 1 of 2
ENSG00000306426	ENST00000818382.1	n.*200A>G		downstream_gene_variant

Frequencies

GnomAD3 genomes AF: 0.524 AC: 79164 AN: 151044 Hom.: 20938 Cov.: 31

Gnomad AFR AF: 0.565

Gnomad AMI AF: 0.372

Gnomad AMR AF: 0.572

Gnomad ASJ AF: 0.447

Gnomad EAS AF: 0.747

Gnomad SAS AF: 0.520

Gnomad FIN AF: 0.559

Gnomad MID AF: 0.439

Gnomad NFE AF: 0.474

Gnomad OTH AF: 0.522

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.524 AC: 79254 AN: 151160 Hom.: 20973 Cov.: 31 AF XY: 0.532 AC XY: 39286 AN XY: 73864

African (AFR) AF: 0.565 AC: 23034 AN: 40742

American (AMR) AF: 0.572 AC: 8700 AN: 15212

Ashkenazi Jewish (ASJ) AF: 0.447 AC: 1551 AN: 3472

East Asian (EAS) AF: 0.747 AC: 3860 AN: 5170

South Asian (SAS) AF: 0.517 AC: 2479 AN: 4794

European-Finnish (FIN) AF: 0.559 AC: 5891 AN: 10544

Middle Eastern (MID) AF: 0.432 AC: 126 AN: 292

European-Non Finnish (NFE) AF: 0.474 AC: 32168 AN: 67920

Other (OTH) AF: 0.526 AC: 1107 AN: 2106

Alfa AF: 0.492 Hom.: 53630

Bravo AF: 0.527

Asia WGS AF: 0.646 AC: 2243 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	3.6
DANN	Benign	0.31
PhyloP100		0.16

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs10491733; hg19: chr9-4483189; COSMIC: COSV53510123;