9-4419154-T-C

Variant names:

• chr9-4419154-T-C
• rs10814969
• XM_047422890.1:c.-152+70474A>G

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+70474A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.487 in 152,034 control chromosomes in the GnomAD database, including 18,538 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 0.49 (18538 hom., cov: 32)
• Consequence: GLIS3 XM_047422890.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.428
• Publications: 3 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=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.537 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: 0.487 AC: 73989 AN: 151916 Hom.: 18518 Cov.: 32

Gnomad AFR AF: 0.449

Gnomad AMI AF: 0.498

Gnomad AMR AF: 0.391

Gnomad ASJ AF: 0.575

Gnomad EAS AF: 0.210

Gnomad SAS AF: 0.514

Gnomad FIN AF: 0.519

Gnomad MID AF: 0.468

Gnomad NFE AF: 0.542

Gnomad OTH AF: 0.483

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

GnomAD4 genome AF: 0.487 AC: 74059 AN: 152034 Hom.: 18538 Cov.: 32 AF XY: 0.484 AC XY: 35974 AN XY: 74320

African (AFR) AF: 0.449 AC: 18588 AN: 41416

American (AMR) AF: 0.390 AC: 5963 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.575 AC: 1994 AN: 3470

East Asian (EAS) AF: 0.210 AC: 1089 AN: 5178

South Asian (SAS) AF: 0.516 AC: 2487 AN: 4822

European-Finnish (FIN) AF: 0.519 AC: 5476 AN: 10556

Middle Eastern (MID) AF: 0.486 AC: 142 AN: 292

European-Non Finnish (NFE) AF: 0.542 AC: 36838 AN: 67986

Other (OTH) AF: 0.486 AC: 1028 AN: 2114

Alfa AF: 0.517 Hom.: 27514

Bravo AF: 0.474

Asia WGS AF: 0.376 AC: 1306 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.6
DANN	Benign	0.46
PhyloP100		0.43

Splicing

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

Other links and lift over

dbSNP: rs10814969; hg19: chr9-4419154; COSMIC: COSV60323233;