9-3824931-AAAAAT-A

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BS1_Supporting BS2

The NM_001042413.2(GLIS3):c.*3336_*3340del variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.0010 (5 hom., cov: 0)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: GLIS3 NM_001042413.2 3_prime_UTR
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.10

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 Likely_benign. Variant got -5 ACMG points.

• BS1: Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.00104 (116/111568) while in subpopulation SAS AF= 0.0356 (106/2978). AF 95% confidence interval is 0.0301. There are 5 homozygotes in gnomad4. There are 86 alleles in male gnomad4 subpopulation. Median coverage is 0. This position pass quality control queck. Existence of Clinvar submissions makes me limit the strength of this signal to Supporting
• BS2: High Homozygotes in GnomAd at 5 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GLIS3	NM_001042413.2	c.*3336_*3340del		3_prime_UTR_variant	11/11	ENST00000381971.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GLIS3	ENST00000381971.8	c.*3336_*3340del		3_prime_UTR_variant	11/11	5	NM_001042413.2	P1

Frequencies

GnomAD3 genomes AF: 0.00106 AC: 118 AN: 111456 Hom.: 5 Cov.: 0

Gnomad AFR AF: 0.000124

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000512

Gnomad SAS AF: 0.0364

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000599

Gnomad OTH AF: 0.000702

GnomAD4 exome Data not reliable, filtered out with message: AC0;AS_VQSR AF: 0.00 AC: 0 AN: 78 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 44

Gnomad4 FIN exome AF: 0.00

GnomAD4 genome AF: 0.00104 AC: 116 AN: 111568 Hom.: 5 Cov.: 0 AF XY: 0.00160 AC XY: 86 AN XY: 53906

Gnomad4 AFR AF: 0.000124

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000513

Gnomad4 SAS AF: 0.0356

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000599

Gnomad4 OTH AF: 0.000692

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

Neonatal diabetes mellitus with congenital hypothyroidism Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

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: rs886063937; hg19: chr9-3824931;