9-3824894-CTTT-CTTTT

Variant names:

• chr9-3824894-C-CT
• rs202118987
• NM_001042413.2:c.*3377dupA

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BA1

The NM_001042413.2(GLIS3):​c.*3377dupA variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0525 in 120,150 control chromosomes in the GnomAD database, including 182 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.052 (182 hom., cov: 23)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: GLIS3 NM_001042413.2 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.373

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 -8 ACMG points.

• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.075 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GLIS3	NM_001042413.2	c.*3377dupA		3_prime_UTR_variant	Exon 11 of 11	ENST00000381971.8	NP_001035878.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GLIS3	ENST00000381971	c.*3377dupA		3_prime_UTR_variant	Exon 11 of 11	5	NM_001042413.2	ENSP00000371398.3

Frequencies

GnomAD3 genomes AF: 0.0525 AC: 6307 AN: 120146 Hom.: 182 Cov.: 23

Gnomad AFR AF: 0.0162

Gnomad AMI AF: 0.0282

Gnomad AMR AF: 0.0468

Gnomad ASJ AF: 0.0643

Gnomad EAS AF: 0.000708

Gnomad SAS AF: 0.0155

Gnomad FIN AF: 0.0668

Gnomad MID AF: 0.0924

Gnomad NFE AF: 0.0769

Gnomad OTH AF: 0.0567

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 28 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 14

Gnomad4 FIN exome AF: 0.00

GnomAD4 genome AF: 0.0525 AC: 6306 AN: 120150 Hom.: 182 Cov.: 23 AF XY: 0.0513 AC XY: 2912 AN XY: 56760

Gnomad4 AFR AF: 0.0162

Gnomad4 AMR AF: 0.0468

Gnomad4 ASJ AF: 0.0643

Gnomad4 EAS AF: 0.000710

Gnomad4 SAS AF: 0.0156

Gnomad4 FIN AF: 0.0668

Gnomad4 NFE AF: 0.0769

Gnomad4 OTH AF: 0.0564

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs202118987; hg19: chr9-3824894;