chr9-4083665-T-G

Position:

• chr9-4083665-T-G

Variant summary

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

The NM_001042413.2(GLIS3):​c.1710+34103A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.41 in 151,988 control chromosomes in the GnomAD database, including 12,693 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 0.41 (12693 hom., cov: 32)
• Consequence: GLIS3 NM_001042413.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.123

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.429 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GLIS3	NM_001042413.2	c.1710+34103A>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.1710+34103A>C		intron_variant		5	NM_001042413.2	ENSP00000371398.3

Frequencies

GnomAD3 genomes AF: 0.410 AC: 62226 AN: 151868 Hom.: 12676 Cov.: 32

Gnomad AFR AF: 0.383

Gnomad AMI AF: 0.330

Gnomad AMR AF: 0.438

Gnomad ASJ AF: 0.471

Gnomad EAS AF: 0.383

Gnomad SAS AF: 0.341

Gnomad FIN AF: 0.413

Gnomad MID AF: 0.358

Gnomad NFE AF: 0.424

Gnomad OTH AF: 0.417

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

GnomAD4 genome AF: 0.410 AC: 62295 AN: 151988 Hom.: 12693 Cov.: 32 AF XY: 0.409 AC XY: 30390 AN XY: 74294

Gnomad4 AFR AF: 0.384

Gnomad4 AMR AF: 0.438

Gnomad4 ASJ AF: 0.471

Gnomad4 EAS AF: 0.383

Gnomad4 SAS AF: 0.342

Gnomad4 FIN AF: 0.413

Gnomad4 NFE AF: 0.424

Gnomad4 OTH AF: 0.415

Alfa AF: 0.424 Hom.: 21949

Bravo AF: 0.411

Asia WGS AF: 0.359 AC: 1251 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	1.8
DANN	Benign	0.43

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: rs6476804; hg19: chr9-4083665;