9-4368838-C-T

Variant names:

• chr9-4368838-C-T
• rs10814948
• XM_047422890.1:c.-151-20426G>A

Variant summary

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

The XM_047422890.1(GLIS3):​c.-151-20426G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.331 in 152,034 control chromosomes in the GnomAD database, including 8,541 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 0.33 (8541 hom., cov: 32)
• Consequence: GLIS3 XM_047422890.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.04

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=-0.93).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.428 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GLIS3	XM_047422890.1	c.-151-20426G>A		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: 0.331 AC: 50254 AN: 151918 Hom.: 8539 Cov.: 32

Gnomad AFR AF: 0.347

Gnomad AMI AF: 0.431

Gnomad AMR AF: 0.284

Gnomad ASJ AF: 0.450

Gnomad EAS AF: 0.356

Gnomad SAS AF: 0.443

Gnomad FIN AF: 0.239

Gnomad MID AF: 0.453

Gnomad NFE AF: 0.328

Gnomad OTH AF: 0.344

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

GnomAD4 genome AF: 0.331 AC: 50263 AN: 152034 Hom.: 8541 Cov.: 32 AF XY: 0.329 AC XY: 24457 AN XY: 74322

Gnomad4 AFR AF: 0.346

Gnomad4 AMR AF: 0.283

Gnomad4 ASJ AF: 0.450

Gnomad4 EAS AF: 0.355

Gnomad4 SAS AF: 0.444

Gnomad4 FIN AF: 0.239

Gnomad4 NFE AF: 0.328

Gnomad4 OTH AF: 0.344

Alfa AF: 0.326 Hom.: 7950

Bravo AF: 0.331

Asia WGS AF: 0.377 AC: 1315 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.32
DANN	Benign	0.81

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs10814948; hg19: chr9-4368838; COSMIC: COSV60323188;