rs954864

Variant names:

• chr9-4476238-G-A
• rs954864
• ENST00000818379.1:n.696+13390C>T

Your query was ambiguous. Multiple possible variants found:

• chr9-4476238-G-A
• chr9-4476238-G-C

Variant summary

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

The ENST00000818379.1(ENSG00000306426):​n.696+13390C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.176 in 152,118 control chromosomes in the GnomAD database, including 2,491 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 0.18 (2491 hom., cov: 32)
• Consequence: ENSG00000306426 ENST00000818379.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0320
• Publications: 2 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=-0.81).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.207 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GLIS3	XM_047422890.1	c.-152+13390C>T		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+13390C>T		intron_variant	Intron 1 of 1
ENSG00000306426	ENST00000818380.1	n.377+13628C>T		intron_variant	Intron 1 of 1
ENSG00000306426	ENST00000818381.1	n.231+13628C>T		intron_variant	Intron 1 of 2

Frequencies

GnomAD3 genomes AF: 0.176 AC: 26701 AN: 152000 Hom.: 2481 Cov.: 32

Gnomad AFR AF: 0.114

Gnomad AMI AF: 0.284

Gnomad AMR AF: 0.213

Gnomad ASJ AF: 0.202

Gnomad EAS AF: 0.143

Gnomad SAS AF: 0.164

Gnomad FIN AF: 0.191

Gnomad MID AF: 0.136

Gnomad NFE AF: 0.202

Gnomad OTH AF: 0.200

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

GnomAD4 genome AF: 0.176 AC: 26725 AN: 152118 Hom.: 2491 Cov.: 32 AF XY: 0.176 AC XY: 13059 AN XY: 74352

African (AFR) AF: 0.114 AC: 4735 AN: 41524

American (AMR) AF: 0.213 AC: 3256 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.202 AC: 701 AN: 3468

East Asian (EAS) AF: 0.143 AC: 740 AN: 5186

South Asian (SAS) AF: 0.164 AC: 788 AN: 4812

European-Finnish (FIN) AF: 0.191 AC: 2013 AN: 10542

Middle Eastern (MID) AF: 0.143 AC: 42 AN: 294

European-Non Finnish (NFE) AF: 0.202 AC: 13752 AN: 67990

Other (OTH) AF: 0.208 AC: 439 AN: 2110

Alfa AF: 0.192 Hom.: 10283

Bravo AF: 0.176

Asia WGS AF: 0.197 AC: 685 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	4.9
DANN	Benign	0.69
PhyloP100		-0.032

Splicing

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

Other links and lift over

dbSNP: rs954864; hg19: chr9-4476238;