rs954864

Variant names:

• chr9-4476238-G-A
• rs954864
• XM_047422890.1:c.-152+13390C>T

Your query was ambiguous. Multiple possible variants found:

• chr9-4476238-G-A
• chr9-4476238-G-C

Variant summary

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

The XM_047422890.1(GLIS3):​c.-152+13390C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.176 in 152,118 control chromosomes in the GnomAD database, including 2,491 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 0.18 (2491 hom., cov: 32)
• Consequence: GLIS3 XM_047422890.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0320

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 (AMR) allele frequency at 95% confidence interval = 0.207 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GLIS3	XM_047422890.1	c.-152+13390C>T		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: 0.176 AC: 26701 AN: 152000 Hom.: 2481 Cov.: 32

Gnomad AFR AF: 0.114

Gnomad AMI AF: 0.284

Gnomad AMR AF: 0.213

Gnomad ASJ AF: 0.202

Gnomad EAS AF: 0.143

Gnomad SAS AF: 0.164

Gnomad FIN AF: 0.191

Gnomad MID AF: 0.136

Gnomad NFE AF: 0.202

Gnomad OTH AF: 0.200

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

GnomAD4 genome AF: 0.176 AC: 26725 AN: 152118 Hom.: 2491 Cov.: 32 AF XY: 0.176 AC XY: 13059 AN XY: 74352

Gnomad4 AFR AF: 0.114

Gnomad4 AMR AF: 0.213

Gnomad4 ASJ AF: 0.202

Gnomad4 EAS AF: 0.143

Gnomad4 SAS AF: 0.164

Gnomad4 FIN AF: 0.191

Gnomad4 NFE AF: 0.202

Gnomad4 OTH AF: 0.208

Alfa AF: 0.194 Hom.: 4713

Bravo AF: 0.176

Asia WGS AF: 0.197 AC: 685 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	4.9
DANN	Benign	0.69

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs954864; hg19: chr9-4476238;