XM_047422890.1:c.-152+62997G>T

Variant names:

• chr9-4426631-C-A
• rs10974531
• XM_047422890.1:c.-152+62997G>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The XM_047422890.1(GLIS3):​c.-152+62997G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.233 in 152,212 control chromosomes in the GnomAD database, including 5,151 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.23 (5151 hom., cov: 33)
• Consequence: GLIS3 XM_047422890.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.274
• Publications: 16 publications found

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]

GLIS3 Gene-Disease associations (from GenCC):

• neonatal diabetes mellitus with congenital hypothyroidism

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Ambry Genetics, Genomics England PanelApp, G2P, Orphanet, Labcorp Genetics (formerly Invitae)
• Tourette syndrome

  Inheritance: Unknown Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.321 is higher than 0.05.

Variant Effect in Transcripts

 

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
There are no transcript annotations for this variant.

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
There are no transcript annotations for this variant.

Frequencies

GnomAD3 genomes AF: 0.233 AC: 35497 AN: 152094 Hom.: 5152 Cov.: 33

Gnomad AFR AF: 0.0694

Gnomad AMI AF: 0.322

Gnomad AMR AF: 0.278

Gnomad ASJ AF: 0.311

Gnomad EAS AF: 0.133

Gnomad SAS AF: 0.275

Gnomad FIN AF: 0.217

Gnomad MID AF: 0.239

Gnomad NFE AF: 0.325

Gnomad OTH AF: 0.252

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.233 AC: 35492 AN: 152212 Hom.: 5151 Cov.: 33 AF XY: 0.229 AC XY: 17059 AN XY: 74426

African (AFR) AF: 0.0692 AC: 2877 AN: 41552

American (AMR) AF: 0.278 AC: 4242 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.311 AC: 1077 AN: 3466

East Asian (EAS) AF: 0.133 AC: 689 AN: 5190

South Asian (SAS) AF: 0.275 AC: 1325 AN: 4822

European-Finnish (FIN) AF: 0.217 AC: 2298 AN: 10592

Middle Eastern (MID) AF: 0.233 AC: 68 AN: 292

European-Non Finnish (NFE) AF: 0.325 AC: 22092 AN: 67992

Other (OTH) AF: 0.251 AC: 531 AN: 2112

Alfa AF: 0.288 Hom.: 15071

Bravo AF: 0.230

Asia WGS AF: 0.206 AC: 716 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.96
DANN	Benign	0.46
PhyloP100		-0.27

Splicing

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

Other links and lift over

dbSNP: rs10974531; hg19: chr9-4426631; COSMIC: COSV50193295;