9-4368838-C-T

Variant names:

• chr9-4368838-C-T
• rs10814948
• XM_047422890.1:c.-151-20426G>A

Variant summary

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

The XM_047422890.1(GLIS3):​c.-151-20426G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.331 in 152,034 control chromosomes in the GnomAD database, including 8,541 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 0.33 (8541 hom., cov: 32)
• Consequence: GLIS3 XM_047422890.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.04
• Publications: 2 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: Orphanet, G2P, Ambry Genetics, Labcorp Genetics (formerly Invitae), Genomics England PanelApp
• 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=-0.93).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.428 is higher than 0.05.

Variant Effect in Transcripts

 

RefSeq Transcripts

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

Ensembl Transcripts

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

Frequencies

GnomAD3 genomes AF: 0.331 AC: 50254 AN: 151918 Hom.: 8539 Cov.: 32

Gnomad AFR AF: 0.347

Gnomad AMI AF: 0.431

Gnomad AMR AF: 0.284

Gnomad ASJ AF: 0.450

Gnomad EAS AF: 0.356

Gnomad SAS AF: 0.443

Gnomad FIN AF: 0.239

Gnomad MID AF: 0.453

Gnomad NFE AF: 0.328

Gnomad OTH AF: 0.344

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

GnomAD4 genome AF: 0.331 AC: 50263 AN: 152034 Hom.: 8541 Cov.: 32 AF XY: 0.329 AC XY: 24457 AN XY: 74322

African (AFR) AF: 0.346 AC: 14352 AN: 41436

American (AMR) AF: 0.283 AC: 4331 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.450 AC: 1558 AN: 3466

East Asian (EAS) AF: 0.355 AC: 1832 AN: 5162

South Asian (SAS) AF: 0.444 AC: 2136 AN: 4810

European-Finnish (FIN) AF: 0.239 AC: 2523 AN: 10576

Middle Eastern (MID) AF: 0.442 AC: 130 AN: 294

European-Non Finnish (NFE) AF: 0.328 AC: 22282 AN: 67982

Other (OTH) AF: 0.344 AC: 727 AN: 2114

Alfa AF: 0.327 Hom.: 10391

Bravo AF: 0.331

Asia WGS AF: 0.377 AC: 1315 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.32
DANN	Benign	0.81
PhyloP100		-1.0

Splicing

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

Other links and lift over

dbSNP: rs10814948; hg19: chr9-4368838; COSMIC: COSV60323188;