rs7851070

Variant names:

• chr9-4170457-A-G
• rs7851070
• NM_001042413.2:c.389-44516T>C

Your query was ambiguous. Multiple possible variants found:

• chr9-4170457-A-G
• chr9-4170457-A-T

Variant summary

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

The NM_001042413.2(GLIS3):​c.389-44516T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.378 in 152,030 control chromosomes in the GnomAD database, including 12,652 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 0.38 (12652 hom., cov: 32)
• Consequence: GLIS3 NM_001042413.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0840
• Publications: 2 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=-0.86).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.64 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GLIS3	NM_001042413.2	c.389-44516T>C		intron_variant	Intron 2 of 10	ENST00000381971.8	NP_001035878.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GLIS3	ENST00000381971.8	c.389-44516T>C		intron_variant	Intron 2 of 10	5	NM_001042413.2	ENSP00000371398.3

Frequencies

GnomAD3 genomes AF: 0.378 AC: 57476 AN: 151912 Hom.: 12645 Cov.: 32

Gnomad AFR AF: 0.146

Gnomad AMI AF: 0.353

Gnomad AMR AF: 0.470

Gnomad ASJ AF: 0.382

Gnomad EAS AF: 0.659

Gnomad SAS AF: 0.429

Gnomad FIN AF: 0.537

Gnomad MID AF: 0.386

Gnomad NFE AF: 0.449

Gnomad OTH AF: 0.408

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

GnomAD4 genome AF: 0.378 AC: 57485 AN: 152030 Hom.: 12652 Cov.: 32 AF XY: 0.386 AC XY: 28675 AN XY: 74296

African (AFR) AF: 0.145 AC: 6040 AN: 41536

American (AMR) AF: 0.470 AC: 7170 AN: 15252

Ashkenazi Jewish (ASJ) AF: 0.382 AC: 1325 AN: 3468

East Asian (EAS) AF: 0.659 AC: 3390 AN: 5148

South Asian (SAS) AF: 0.430 AC: 2065 AN: 4806

European-Finnish (FIN) AF: 0.537 AC: 5665 AN: 10554

Middle Eastern (MID) AF: 0.388 AC: 114 AN: 294

European-Non Finnish (NFE) AF: 0.449 AC: 30525 AN: 67948

Other (OTH) AF: 0.412 AC: 870 AN: 2114

Alfa AF: 0.434 Hom.: 9547

Bravo AF: 0.368

Asia WGS AF: 0.505 AC: 1756 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	4.3
DANN	Benign	0.69
PhyloP100		0.084
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: rs7851070; hg19: chr9-4170457; COSMIC: COSV67942740;