chr9-4144958-A-C

Position:

• chr9-4144958-A-C

Variant summary

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

The ENST00000462164.5(GLIS3):​c.-197T>G variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.229 in 152,228 control chromosomes in the GnomAD database, including 4,179 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 0.23 (4179 hom., cov: 33)
  • Failed GnomAD Quality Control
• Consequence: GLIS3 ENST00000462164.5 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.348

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=-0.85).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.263 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GLIS3	NM_001042413.2	c.389-19017T>G		intron_variant		ENST00000381971.8	NP_001035878.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GLIS3	ENST00000381971.8	c.389-19017T>G		intron_variant		5	NM_001042413.2	ENSP00000371398.3

Frequencies

GnomAD3 genomes AF: 0.229 AC: 34855 AN: 152110 Hom.: 4163 Cov.: 33

Gnomad AFR AF: 0.175

Gnomad AMI AF: 0.129

Gnomad AMR AF: 0.270

Gnomad ASJ AF: 0.249

Gnomad EAS AF: 0.204

Gnomad SAS AF: 0.239

Gnomad FIN AF: 0.252

Gnomad MID AF: 0.250

Gnomad NFE AF: 0.250

Gnomad OTH AF: 0.243

GnomAD4 exome Data not reliable, filtered out with message: AC0 AC: 0 AN: 0 Hom.: 0 Cov.: 0 AC XY: 0 AN XY: 0

GnomAD4 genome AF: 0.229 AC: 34897 AN: 152228 Hom.: 4179 Cov.: 33 AF XY: 0.230 AC XY: 17136 AN XY: 74414

Gnomad4 AFR AF: 0.176

Gnomad4 AMR AF: 0.270

Gnomad4 ASJ AF: 0.249

Gnomad4 EAS AF: 0.204

Gnomad4 SAS AF: 0.238

Gnomad4 FIN AF: 0.252

Gnomad4 NFE AF: 0.250

Gnomad4 OTH AF: 0.246

Alfa AF: 0.243 Hom.: 2189

Bravo AF: 0.230

Asia WGS AF: 0.243 AC: 844 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	9.8
DANN	Benign	0.63

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: rs10491552; hg19: chr9-4144958;