chr9-4482706-T-C

Variant names:

• chr9-4482706-T-C
• rs10491734
• XM_047422890.1:c.-152+6922A>G

Variant summary

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

The XM_047422890.1(GLIS3):​c.-152+6922A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.663 in 152,160 control chromosomes in the GnomAD database, including 34,725 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 0.66 (34725 hom., cov: 33)
• Consequence: GLIS3 XM_047422890.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.122

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=-0.81).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.85 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GLIS3	XM_047422890.1	c.-152+6922A>G		intron_variant	Intron 1 of 11		XP_047278846.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt

Frequencies

GnomAD3 genomes AF: 0.663 AC: 100837 AN: 152042 Hom.: 34680 Cov.: 33

Gnomad AFR AF: 0.857

Gnomad AMI AF: 0.441

Gnomad AMR AF: 0.680

Gnomad ASJ AF: 0.592

Gnomad EAS AF: 0.755

Gnomad SAS AF: 0.612

Gnomad FIN AF: 0.599

Gnomad MID AF: 0.525

Gnomad NFE AF: 0.555

Gnomad OTH AF: 0.660

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

GnomAD4 genome AF: 0.663 AC: 100939 AN: 152160 Hom.: 34725 Cov.: 33 AF XY: 0.665 AC XY: 49477 AN XY: 74368

Gnomad4 AFR AF: 0.857

Gnomad4 AMR AF: 0.680

Gnomad4 ASJ AF: 0.592

Gnomad4 EAS AF: 0.755

Gnomad4 SAS AF: 0.609

Gnomad4 FIN AF: 0.599

Gnomad4 NFE AF: 0.555

Gnomad4 OTH AF: 0.661

Alfa AF: 0.574 Hom.: 32378

Bravo AF: 0.677

Asia WGS AF: 0.707 AC: 2457 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	4.3
DANN	Benign	0.73

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs10491734; hg19: chr9-4482706;