rs10814916

chr9-4293150-A-C

Variant summary

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

The NM_001042413.2(GLIS3):c.-99+6271T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.564 in 152,072 control chromosomes in the GnomAD database, including 24,606 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 0.56 (24606 hom., cov: 33)
• Consequence: GLIS3 NM_001042413.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.618

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=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.67 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GLIS3	NM_001042413.2	c.-99+6271T>G		intron_variant		ENST00000381971.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GLIS3	ENST00000381971.8	c.-99+6271T>G		intron_variant		5	NM_001042413.2	P1

Frequencies

GnomAD3 genomes AF: 0.564 AC: 85679 AN: 151954 Hom.: 24565 Cov.: 33

Gnomad AFR AF: 0.677

Gnomad AMI AF: 0.637

Gnomad AMR AF: 0.531

Gnomad ASJ AF: 0.575

Gnomad EAS AF: 0.462

Gnomad SAS AF: 0.551

Gnomad FIN AF: 0.526

Gnomad MID AF: 0.589

Gnomad NFE AF: 0.516

Gnomad OTH AF: 0.556

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

GnomAD4 genome AF: 0.564 AC: 85768 AN: 152072 Hom.: 24606 Cov.: 33 AF XY: 0.564 AC XY: 41909 AN XY: 74336

Gnomad4 AFR AF: 0.677

Gnomad4 AMR AF: 0.530

Gnomad4 ASJ AF: 0.575

Gnomad4 EAS AF: 0.462

Gnomad4 SAS AF: 0.551

Gnomad4 FIN AF: 0.526

Gnomad4 NFE AF: 0.516

Gnomad4 OTH AF: 0.560

Alfa AF: 0.534 Hom.: 9685

Bravo AF: 0.570

Asia WGS AF: 0.531 AC: 1847 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
Cadd	Benign	1.2
Dann	Benign	0.61

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: rs10814916; hg19: chr9-4293150;