9-4482706-T-C

Variant names:

• chr9-4482706-T-C
• rs10491734
• XM_047422890.1:c.-152+6922A>G

Variant summary

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

The ENST00000818379.1(ENSG00000306426):​n.696+6922A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.663 in 152,160 control chromosomes in the GnomAD database, including 34,725 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 0.66 (34725 hom., cov: 33)
• Consequence: ENSG00000306426 ENST00000818379.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.122
• Publications: 14 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)

ENSG00000306426 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.85 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000818379.1. You can select a different transcript below to see updated ACMG assignments.

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
	ENSG00000306426	ENST00000818379.1		n.696+6922A>G		intron	N/A
	ENSG00000306426	ENST00000818380.1		n.377+7160A>G		intron	N/A
	ENSG00000306426	ENST00000818381.1		n.231+7160A>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.663 AC: 100837 AN: 152042 Hom.: 34680 Cov.: 33

Gnomad AFR AF: 0.857

Gnomad AMI AF: 0.441

Gnomad AMR AF: 0.680

Gnomad ASJ AF: 0.592

Gnomad EAS AF: 0.755

Gnomad SAS AF: 0.612

Gnomad FIN AF: 0.599

Gnomad MID AF: 0.525

Gnomad NFE AF: 0.555

Gnomad OTH AF: 0.660

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

GnomAD4 genome AF: 0.663 AC: 100939 AN: 152160 Hom.: 34725 Cov.: 33 AF XY: 0.665 AC XY: 49477 AN XY: 74368

African (AFR) AF: 0.857 AC: 35609 AN: 41532

American (AMR) AF: 0.680 AC: 10393 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.592 AC: 2053 AN: 3468

East Asian (EAS) AF: 0.755 AC: 3912 AN: 5184

South Asian (SAS) AF: 0.609 AC: 2940 AN: 4824

European-Finnish (FIN) AF: 0.599 AC: 6328 AN: 10568

Middle Eastern (MID) AF: 0.520 AC: 153 AN: 294

European-Non Finnish (NFE) AF: 0.555 AC: 37753 AN: 67978

Other (OTH) AF: 0.661 AC: 1397 AN: 2112

Alfa AF: 0.589 Hom.: 48377

Bravo AF: 0.677

Asia WGS AF: 0.707 AC: 2457 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	4.3
DANN	Benign	0.73
PhyloP100		-0.12

Splicing

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

Other links and lift over

dbSNP: rs10491734; hg19: chr9-4482706;