9-3824934-AAT-A

Position:

• chr9-3824934-AAT-A

Variant summary

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

The NM_001042413.2(GLIS3):​c.*3336_*3337del variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.535 in 123,496 control chromosomes in the GnomAD database, including 16,835 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.54 (16833 hom., cov: 0)
  • Exomes 𝑓: 0.38 (2 hom.)
• Consequence: GLIS3 NM_001042413.2 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:2
• 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 Benign. Variant got -10 ACMG points.

• BP6: Variant 9-3824934-AAT-A is Benign according to our data. Variant chr9-3824934-AAT-A is described in ClinVar as [Benign]. Clinvar id is 366891.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.621 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GLIS3	NM_001042413.2	c.*3336_*3337del		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.*3336_*3337del		3_prime_UTR_variant	11/11	5	NM_001042413.2	ENSP00000371398	P1

Frequencies

GnomAD3 genomes AF: 0.535 AC: 66065 AN: 123470 Hom.: 16829 Cov.: 0

Gnomad AFR AF: 0.397

Gnomad AMI AF: 0.634

Gnomad AMR AF: 0.570

Gnomad ASJ AF: 0.517

Gnomad EAS AF: 0.640

Gnomad SAS AF: 0.640

Gnomad FIN AF: 0.576

Gnomad MID AF: 0.464

Gnomad NFE AF: 0.578

Gnomad OTH AF: 0.549

GnomAD4 exome AF: 0.375 AC: 9 AN: 24 Hom.: 2 AF XY: 0.500 AC XY: 7 AN XY: 14

Gnomad4 FIN exome AF: 0.375

GnomAD4 genome AF: 0.535 AC: 66065 AN: 123472 Hom.: 16833 Cov.: 0 AF XY: 0.536 AC XY: 31623 AN XY: 59024

Gnomad4 AFR AF: 0.397

Gnomad4 AMR AF: 0.570

Gnomad4 ASJ AF: 0.517

Gnomad4 EAS AF: 0.640

Gnomad4 SAS AF: 0.639

Gnomad4 FIN AF: 0.576

Gnomad4 NFE AF: 0.578

Gnomad4 OTH AF: 0.552

Alfa AF: 0.386 Hom.: 114

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, single submitter

Submissions by phenotype

Neonatal diabetes mellitus with congenital hypothyroidism Benign:2

Benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jun 14, 2016	- -
Benign, 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: rs66766243; hg19: chr9-3824934;