9-4419154-T-C

Variant names:

• chr9-4419154-T-C
• rs10814969
• XM_047422890.1:c.-152+70474A>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+70474A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.487 in 152,034 control chromosomes in the GnomAD database, including 18,538 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 0.49 (18538 hom., cov: 32)
• Consequence: GLIS3 XM_047422890.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.428

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=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.537 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GLIS3	XM_047422890.1	c.-152+70474A>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: 0.487 AC: 73989 AN: 151916 Hom.: 18518 Cov.: 32

Gnomad AFR AF: 0.449

Gnomad AMI AF: 0.498

Gnomad AMR AF: 0.391

Gnomad ASJ AF: 0.575

Gnomad EAS AF: 0.210

Gnomad SAS AF: 0.514

Gnomad FIN AF: 0.519

Gnomad MID AF: 0.468

Gnomad NFE AF: 0.542

Gnomad OTH AF: 0.483

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

GnomAD4 genome AF: 0.487 AC: 74059 AN: 152034 Hom.: 18538 Cov.: 32 AF XY: 0.484 AC XY: 35974 AN XY: 74320

Gnomad4 AFR AF: 0.449

Gnomad4 AMR AF: 0.390

Gnomad4 ASJ AF: 0.575

Gnomad4 EAS AF: 0.210

Gnomad4 SAS AF: 0.516

Gnomad4 FIN AF: 0.519

Gnomad4 NFE AF: 0.542

Gnomad4 OTH AF: 0.486

Alfa AF: 0.522 Hom.: 20230

Bravo AF: 0.474

Asia WGS AF: 0.376 AC: 1306 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.6
DANN	Benign	0.46

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs10814969; hg19: chr9-4419154; COSMIC: COSV60323233;