rs7034200

Positions:

• chr9-4289050-C-A
• chr9-4289050-C-G
• chr9-4289050-C-T

Variant summary

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

The NM_001042413.2(GLIS3):​c.-98-2527G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.534 in 151,928 control chromosomes in the GnomAD database, including 22,022 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 0.53 (22022 hom., cov: 32)
• Consequence: GLIS3 NM_001042413.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.470

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=-0.97).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.627 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GLIS3	NM_001042413.2	c.-98-2527G>T		intron_variant		ENST00000381971.8	NP_001035878.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GLIS3	ENST00000381971.8	c.-98-2527G>T		intron_variant		5	NM_001042413.2	ENSP00000371398	P1

Frequencies

GnomAD3 genomes AF: 0.534 AC: 81109 AN: 151812 Hom.: 22001 Cov.: 32

Gnomad AFR AF: 0.634

Gnomad AMI AF: 0.628

Gnomad AMR AF: 0.516

Gnomad ASJ AF: 0.543

Gnomad EAS AF: 0.444

Gnomad SAS AF: 0.535

Gnomad FIN AF: 0.495

Gnomad MID AF: 0.544

Gnomad NFE AF: 0.489

Gnomad OTH AF: 0.527

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

GnomAD4 genome AF: 0.534 AC: 81170 AN: 151928 Hom.: 22022 Cov.: 32 AF XY: 0.535 AC XY: 39745 AN XY: 74248

Gnomad4 AFR AF: 0.633

Gnomad4 AMR AF: 0.515

Gnomad4 ASJ AF: 0.543

Gnomad4 EAS AF: 0.444

Gnomad4 SAS AF: 0.537

Gnomad4 FIN AF: 0.495

Gnomad4 NFE AF: 0.489

Gnomad4 OTH AF: 0.529

Alfa AF: 0.493 Hom.: 34982

Bravo AF: 0.540

Asia WGS AF: 0.505 AC: 1754 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	3.5
DANN	Benign	0.16

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: rs7034200; hg19: chr9-4289050;