NM_001042413.2:c.-98-3286C>A

Variant names:

• chr9-4289809-G-T
• rs2380949
• NM_001042413.2:c.-98-3286C>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.-98-3286C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.837 in 152,138 control chromosomes in the GnomAD database, including 54,327 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 0.84 (54327 hom., cov: 33)
• Consequence: GLIS3 NM_001042413.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.587
• Publications: 8 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=-0.85).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.939 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001042413.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GLIS3	NM_001042413.2	MANE Select	c.-98-3286C>A		intron	N/A	NP_001035878.1
	GLIS3	NM_001438906.1		c.-98-3286C>A		intron	N/A	NP_001425835.1
	GLIS3	NM_001438907.1		c.-98-3286C>A		intron	N/A	NP_001425836.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GLIS3	ENST00000381971.8	TSL:5 MANE Select	c.-98-3286C>A		intron	N/A	ENSP00000371398.3
	GLIS3	ENST00000477901.5	TSL:1	c.-98-3286C>A		intron	N/A	ENSP00000417794.1
	GLIS3	ENST00000481827.5	TSL:1	c.-98-3286C>A		intron	N/A	ENSP00000417883.1

Frequencies

GnomAD3 genomes AF: 0.837 AC: 127297 AN: 152020 Hom.: 54302 Cov.: 33

Gnomad AFR AF: 0.653

Gnomad AMI AF: 0.976

Gnomad AMR AF: 0.878

Gnomad ASJ AF: 0.911

Gnomad EAS AF: 0.961

Gnomad SAS AF: 0.915

Gnomad FIN AF: 0.922

Gnomad MID AF: 0.877

Gnomad NFE AF: 0.906

Gnomad OTH AF: 0.866

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

GnomAD4 genome AF: 0.837 AC: 127367 AN: 152138 Hom.: 54327 Cov.: 33 AF XY: 0.842 AC XY: 62664 AN XY: 74390

African (AFR) AF: 0.653 AC: 27067 AN: 41468

American (AMR) AF: 0.878 AC: 13423 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.911 AC: 3160 AN: 3468

East Asian (EAS) AF: 0.961 AC: 4991 AN: 5194

South Asian (SAS) AF: 0.914 AC: 4409 AN: 4822

European-Finnish (FIN) AF: 0.922 AC: 9783 AN: 10610

Middle Eastern (MID) AF: 0.884 AC: 260 AN: 294

European-Non Finnish (NFE) AF: 0.906 AC: 61552 AN: 67958

Other (OTH) AF: 0.866 AC: 1832 AN: 2116

Alfa AF: 0.832 Hom.: 3418

Bravo AF: 0.827

Asia WGS AF: 0.903 AC: 3141 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	2.6
DANN	Benign	0.42
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: rs2380949; hg19: chr9-4289809;