9-3824894-CT-C

Position:

• chr9-3824894-CT-C

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_001042413.2(GLIS3):​c.*3377del variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.163 in 119,988 control chromosomes in the GnomAD database, including 1,347 homozygotes. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.16 (1347 hom., cov: 23)
  • Exomes 𝑓: 0.14 (0 hom.)
• Consequence: GLIS3 NM_001042413.2 3_prime_UTR
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• 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 -10 ACMG points.

• BP6: Variant 9-3824894-CT-C is Benign according to our data. Variant chr9-3824894-CT-C is described in ClinVar as [Likely_benign]. Clinvar id is 366887.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.18 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GLIS3	NM_001042413.2	c.*3377del		3_prime_UTR_variant	11/11	ENST00000381971.8	NP_001035878.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GLIS3	ENST00000381971.8	c.*3377del		3_prime_UTR_variant	11/11	5	NM_001042413.2	ENSP00000371398	P1

Frequencies

GnomAD3 genomes AF: 0.163 AC: 19543 AN: 119956 Hom.: 1346 Cov.: 23

Gnomad AFR AF: 0.172

Gnomad AMI AF: 0.138

Gnomad AMR AF: 0.158

Gnomad ASJ AF: 0.164

Gnomad EAS AF: 0.191

Gnomad SAS AF: 0.157

Gnomad FIN AF: 0.190

Gnomad MID AF: 0.125

Gnomad NFE AF: 0.156

Gnomad OTH AF: 0.157

GnomAD4 exome AF: 0.143 AC: 4 AN: 28 Hom.: 0 Cov.: 0 AF XY: 0.143 AC XY: 2 AN XY: 14

Gnomad4 FIN exome AF: 0.143

GnomAD4 genome AF: 0.163 AC: 19538 AN: 119960 Hom.: 1347 Cov.: 23 AF XY: 0.166 AC XY: 9378 AN XY: 56660

Gnomad4 AFR AF: 0.172

Gnomad4 AMR AF: 0.158

Gnomad4 ASJ AF: 0.164

Gnomad4 EAS AF: 0.191

Gnomad4 SAS AF: 0.158

Gnomad4 FIN AF: 0.190

Gnomad4 NFE AF: 0.156

Gnomad4 OTH AF: 0.157

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Neonatal diabetes mellitus with congenital hypothyroidism Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

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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;