rs717423

Variant names:

• chr9-3844061-G-A
• rs717423
• NM_001042413.2:c.2473+11948C>T

Your query was ambiguous. Multiple possible variants found:

• chr9-3844061-G-A
• chr9-3844061-G-C

Variant summary

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

The NM_001042413.2(GLIS3):​c.2473+11948C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.215 in 152,086 control chromosomes in the GnomAD database, including 4,109 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 0.21 (4109 hom., cov: 32)
• Consequence: GLIS3 NM_001042413.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.00100
• Publications: 6 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 (NFE) allele frequency at 95% confidence interval = 0.278 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GLIS3	NM_001042413.2	c.2473+11948C>T		intron_variant	Intron 9 of 10	ENST00000381971.8	NP_001035878.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GLIS3	ENST00000381971.8	c.2473+11948C>T		intron_variant	Intron 9 of 10	5	NM_001042413.2	ENSP00000371398.3

Frequencies

GnomAD3 genomes AF: 0.215 AC: 32655 AN: 151968 Hom.: 4109 Cov.: 32

Gnomad AFR AF: 0.0798

Gnomad AMI AF: 0.413

Gnomad AMR AF: 0.231

Gnomad ASJ AF: 0.309

Gnomad EAS AF: 0.185

Gnomad SAS AF: 0.163

Gnomad FIN AF: 0.277

Gnomad MID AF: 0.291

Gnomad NFE AF: 0.281

Gnomad OTH AF: 0.247

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

GnomAD4 genome AF: 0.215 AC: 32652 AN: 152086 Hom.: 4109 Cov.: 32 AF XY: 0.214 AC XY: 15927 AN XY: 74318

African (AFR) AF: 0.0796 AC: 3305 AN: 41500

American (AMR) AF: 0.230 AC: 3522 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.309 AC: 1071 AN: 3468

East Asian (EAS) AF: 0.184 AC: 956 AN: 5186

South Asian (SAS) AF: 0.163 AC: 787 AN: 4822

European-Finnish (FIN) AF: 0.277 AC: 2925 AN: 10550

Middle Eastern (MID) AF: 0.299 AC: 88 AN: 294

European-Non Finnish (NFE) AF: 0.281 AC: 19104 AN: 67960

Other (OTH) AF: 0.245 AC: 517 AN: 2112

Alfa AF: 0.257 Hom.: 3346

Bravo AF: 0.206

Asia WGS AF: 0.147 AC: 514 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	5.2
DANN	Benign	0.62
PhyloP100		-0.0010
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: rs717423; hg19: chr9-3844061;