9-3898987-A-G

Position:

• chr9-3898987-A-G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001042413.2(GLIS3):​c.1984-152T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.792 in 901,986 control chromosomes in the GnomAD database, including 283,466 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.78 (46233 hom., cov: 32)
  • Exomes 𝑓: 0.79 (237233 hom.)
• Consequence: GLIS3 NM_001042413.2 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.483

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-AS1 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BP6: Variant 9-3898987-A-G is Benign according to our data. Variant chr9-3898987-A-G is described in ClinVar as [Benign]. Clinvar id is 1273256.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.813 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GLIS3	NM_001042413.2	c.1984-152T>C		intron_variant		ENST00000381971.8	NP_001035878.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GLIS3	ENST00000381971.8	c.1984-152T>C		intron_variant		5	NM_001042413.2	ENSP00000371398.3

Frequencies

GnomAD3 genomes AF: 0.780 AC: 118463 AN: 151966 Hom.: 46214 Cov.: 32

Gnomad AFR AF: 0.736

Gnomad AMI AF: 0.843

Gnomad AMR AF: 0.816

Gnomad ASJ AF: 0.757

Gnomad EAS AF: 0.834

Gnomad SAS AF: 0.803

Gnomad FIN AF: 0.755

Gnomad MID AF: 0.771

Gnomad NFE AF: 0.796

Gnomad OTH AF: 0.781

GnomAD4 exome AF: 0.794 AC: 595511 AN: 749902 Hom.: 237233 Cov.: 10 AF XY: 0.794 AC XY: 310451 AN XY: 391074

Gnomad4 AFR exome AF: 0.732

Gnomad4 AMR exome AF: 0.842

Gnomad4 ASJ exome AF: 0.755

Gnomad4 EAS exome AF: 0.856

Gnomad4 SAS exome AF: 0.796

Gnomad4 FIN exome AF: 0.775

Gnomad4 NFE exome AF: 0.792

Gnomad4 OTH exome AF: 0.792

GnomAD4 genome AF: 0.779 AC: 118517 AN: 152084 Hom.: 46233 Cov.: 32 AF XY: 0.778 AC XY: 57859 AN XY: 74344

Gnomad4 AFR AF: 0.735

Gnomad4 AMR AF: 0.816

Gnomad4 ASJ AF: 0.757

Gnomad4 EAS AF: 0.834

Gnomad4 SAS AF: 0.803

Gnomad4 FIN AF: 0.755

Gnomad4 NFE AF: 0.796

Gnomad4 OTH AF: 0.783

Alfa AF: 0.790 Hom.: 46026

Bravo AF: 0.781

Asia WGS AF: 0.832 AC: 2892 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 12, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	8.9
DANN	Benign	0.52

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: rs10122183; hg19: chr9-3898987; COSMIC: COSV60926185;