chr9-3824934-A-AT

Position:

• chr9-3824934-A-AT

Variant summary

Our verdict is Likely benign. Variant got -1 ACMG points: 0P and 1B. BS1_Supporting

The NM_001042413.2(GLIS3):​c.*3337_*3338insA 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 0.00039 (1 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: 0.652

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 -1 ACMG points.

• BS1: Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.000395 (49/124072) while in subpopulation SAS AF= 0.000717 (3/4186). AF 95% confidence interval is 0.00025. There are 1 homozygotes in gnomad4. There are 21 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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GLIS3	NM_001042413.2	c.*3337_*3338insA		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.*3337_*3338insA		3_prime_UTR_variant	11/11	5	NM_001042413.2	ENSP00000371398	P1

Frequencies

GnomAD3 genomes AF: 0.000395 AC: 49 AN: 124070 Hom.: 1 Cov.: 0

Gnomad AFR AF: 0.000424

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000316

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000646

Gnomad SAS AF: 0.000714

Gnomad FIN AF: 0.000835

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000349

Gnomad OTH AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 24 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 14

Gnomad4 FIN exome AF: 0.00

GnomAD4 genome AF: 0.000395 AC: 49 AN: 124072 Hom.: 1 Cov.: 0 AF XY: 0.000354 AC XY: 21 AN XY: 59336

Gnomad4 AFR AF: 0.000424

Gnomad4 AMR AF: 0.000316

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000648

Gnomad4 SAS AF: 0.000717

Gnomad4 FIN AF: 0.000835

Gnomad4 NFE AF: 0.000349

Gnomad4 OTH AF: 0.00

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: rs886063938; hg19: chr9-3824934;