rs10758594

Variant names:

• chr9-4295583-A-G
• rs10758594
• NM_001042413.2:c.-99+3838T>C

Your query was ambiguous. Multiple possible variants found:

• chr9-4295583-A-G
• chr9-4295583-A-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001042413.2(GLIS3):​c.-99+3838T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.456 in 151,984 control chromosomes in the GnomAD database, including 17,292 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 (17292 hom., cov: 32)
• Consequence: GLIS3 NM_001042413.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.20

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.565 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GLIS3	NM_001042413.2	c.-99+3838T>C		intron_variant	Intron 1 of 10	ENST00000381971.8	NP_001035878.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GLIS3	ENST00000381971.8	c.-99+3838T>C		intron_variant	Intron 1 of 10	5	NM_001042413.2	ENSP00000371398.3

Frequencies

GnomAD3 genomes AF: 0.456 AC: 69248 AN: 151864 Hom.: 17291 Cov.: 32

Gnomad AFR AF: 0.244

Gnomad AMI AF: 0.396

Gnomad AMR AF: 0.445

Gnomad ASJ AF: 0.492

Gnomad EAS AF: 0.446

Gnomad SAS AF: 0.480

Gnomad FIN AF: 0.556

Gnomad MID AF: 0.484

Gnomad NFE AF: 0.569

Gnomad OTH AF: 0.474

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

GnomAD4 genome AF: 0.456 AC: 69286 AN: 151984 Hom.: 17292 Cov.: 32 AF XY: 0.456 AC XY: 33852 AN XY: 74282

Gnomad4 AFR AF: 0.244

Gnomad4 AMR AF: 0.446

Gnomad4 ASJ AF: 0.492

Gnomad4 EAS AF: 0.446

Gnomad4 SAS AF: 0.479

Gnomad4 FIN AF: 0.556

Gnomad4 NFE AF: 0.569

Gnomad4 OTH AF: 0.471

Alfa AF: 0.537 Hom.: 28553

Bravo AF: 0.439

Asia WGS AF: 0.456 AC: 1585 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.064
DANN	Benign	0.41

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

Publications

LitVar

Other links and lift over

dbSNP: rs10758594; hg19: chr9-4295583; COSMIC: COSV67943002; COSMIC: COSV67943002;