rs10814831

Variant names:

• chr9-4083863-T-C
• rs10814831
• NM_001042413.2:c.1710+33905A>G

Your query was ambiguous. Multiple possible variants found:

• chr9-4083863-T-C
• chr9-4083863-T-G

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+33905A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.254 in 152,146 control chromosomes in the GnomAD database, including 5,266 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 0.25 (5266 hom., cov: 32)
• Consequence: GLIS3 NM_001042413.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.420
• Publications: 5 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=-0.87).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.367 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.1710+33905A>G		intron	N/A	NP_001035878.1
	GLIS3	NM_001438906.1		c.1710+33905A>G		intron	N/A	NP_001425835.1
	GLIS3	NM_001438907.1		c.1710+33905A>G		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.1710+33905A>G		intron	N/A	ENSP00000371398.3
	GLIS3	ENST00000324333.14	TSL:1	c.1245+33905A>G		intron	N/A	ENSP00000325494.10
	GLIS3	ENST00000467497.6	TSL:1	n.250+33905A>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.254 AC: 38602 AN: 152028 Hom.: 5259 Cov.: 32

Gnomad AFR AF: 0.149

Gnomad AMI AF: 0.189

Gnomad AMR AF: 0.294

Gnomad ASJ AF: 0.298

Gnomad EAS AF: 0.381

Gnomad SAS AF: 0.263

Gnomad FIN AF: 0.323

Gnomad MID AF: 0.237

Gnomad NFE AF: 0.286

Gnomad OTH AF: 0.254

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

GnomAD4 genome AF: 0.254 AC: 38644 AN: 152146 Hom.: 5266 Cov.: 32 AF XY: 0.257 AC XY: 19106 AN XY: 74384

African (AFR) AF: 0.150 AC: 6211 AN: 41532

American (AMR) AF: 0.294 AC: 4500 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.298 AC: 1033 AN: 3472

East Asian (EAS) AF: 0.381 AC: 1971 AN: 5176

South Asian (SAS) AF: 0.265 AC: 1277 AN: 4818

European-Finnish (FIN) AF: 0.323 AC: 3413 AN: 10570

Middle Eastern (MID) AF: 0.248 AC: 73 AN: 294

European-Non Finnish (NFE) AF: 0.286 AC: 19458 AN: 67970

Other (OTH) AF: 0.254 AC: 536 AN: 2112

Alfa AF: 0.251 Hom.: 2332

Bravo AF: 0.249

Asia WGS AF: 0.307 AC: 1069 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	2.1
DANN	Benign	0.65
PhyloP100		-0.42
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: rs10814831; hg19: chr9-4083863;