rs806031

Variant names:

• chr9-4100236-C-T
• rs806031
• NM_001042413.2:c.1710+17532G>A

Variant summary

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

The NM_001042413.2(GLIS3):​c.1710+17532G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.462 in 152,018 control chromosomes in the GnomAD database, including 17,084 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 0.46 (17084 hom., cov: 32)
• Consequence: GLIS3 NM_001042413.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.592
• Publications: 3 publications found

Genes affected

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=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.62 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GLIS3	NM_001042413.2	c.1710+17532G>A		intron_variant	Intron 4 of 10	ENST00000381971.8	NP_001035878.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GLIS3	ENST00000381971.8	c.1710+17532G>A		intron_variant	Intron 4 of 10	5	NM_001042413.2	ENSP00000371398.3

Frequencies

GnomAD3 genomes AF: 0.461 AC: 70100 AN: 151898 Hom.: 17051 Cov.: 32

Gnomad AFR AF: 0.626

Gnomad AMI AF: 0.373

Gnomad AMR AF: 0.416

Gnomad ASJ AF: 0.457

Gnomad EAS AF: 0.501

Gnomad SAS AF: 0.322

Gnomad FIN AF: 0.380

Gnomad MID AF: 0.516

Gnomad NFE AF: 0.392

Gnomad OTH AF: 0.454

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

GnomAD4 genome AF: 0.462 AC: 70197 AN: 152018 Hom.: 17084 Cov.: 32 AF XY: 0.460 AC XY: 34163 AN XY: 74306

African (AFR) AF: 0.627 AC: 25988 AN: 41460

American (AMR) AF: 0.416 AC: 6343 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.457 AC: 1585 AN: 3468

East Asian (EAS) AF: 0.501 AC: 2588 AN: 5170

South Asian (SAS) AF: 0.323 AC: 1558 AN: 4818

European-Finnish (FIN) AF: 0.380 AC: 4018 AN: 10578

Middle Eastern (MID) AF: 0.510 AC: 150 AN: 294

European-Non Finnish (NFE) AF: 0.393 AC: 26674 AN: 67948

Other (OTH) AF: 0.452 AC: 953 AN: 2110

Alfa AF: 0.416 Hom.: 57574

Bravo AF: 0.475

Asia WGS AF: 0.386 AC: 1343 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	2.7
DANN	Benign	0.62
PhyloP100		0.59
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: rs806031; hg19: chr9-4100236; COSMIC: COSV60935081;